1
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Zhu S, Pan W, Yao Y, Shi K. The efficacy of colchicine compared to placebo for preventing ischemic stroke among individuals with established atherosclerotic cardiovascular diseases: a systematic review and meta-analysis. SCAND CARDIOVASC J 2025; 59:2441112. [PMID: 39689934 DOI: 10.1080/14017431.2024.2441112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 01/12/2024] [Accepted: 02/07/2024] [Indexed: 12/19/2024]
Abstract
Background. Colchicine is an anti-inflammatory drug with promising efficacy for preventing cardiovascular events. We aimed to assess the pooled effect of colchicine on ischemic stroke among patients with established atherosclerotic cardiovascular diseases. Methods. PubMed, Scopus, Web of Science, and the Cochrane Library were systematically searched from the inception to August 5, 2024. A random-effects (DerSimonian-Laird) model was used to conduct this meta-analysis. The inclusion criteria were as follows: (I) being a randomized controlled trial; and (II) measuring the efficacy of colchicine compared to placebo for preventing ischemic stroke among those with established atherosclerotic cardiovascular diseases. Results. We identified 13 eligible clinical trials with 24900 participants. Colchicine significantly decreased the risk of ischemic stroke (relative risk (RR) 0.85, 95% confidence interval (CI) (0.72, 0.99), I2=2.92%) among those with established atherosclerotic cardiovascular diseases. Colchicine was more effective when used at 0.5 mg/day (RR 0.86, 95% CI (0.75, 0.99)), prescribed for more than 30 days (RR 0.86, 95% CI (0.75, 1.00)) or for more than 90 days (RR 0.65, 95% CI (0.46, 0.92)), or administered for patients with acute coronary syndrome (RR 0.46, 95% CI (0.23, 0.92)). In addition, colchicine was more effective in studies with a sample size of more than 500 patients, consistent with sensitivity analysis, which indicated that the results relied on large-sized clinical trials. Conclusion. Colchicine may decrease the risk of ischemic stroke among patients with established atherosclerotic cardiovascular diseases, particularly after long-term use; however, future studies are needed due to inconsistencies between existing trials.
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Affiliation(s)
- Shulai Zhu
- Department of Neurology, The Second Hospital of Liaocheng Affiliated to Shandong First Medical University, Linqing, China
| | - Weiwei Pan
- Department of Cadre Health Care, Qingdao Municipal Hospital, Qingdao, China
| | - Yingjie Yao
- Department of Cardiology, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao, China
| | - Kai Shi
- Department of Cadre Health Care, Qingdao Municipal Hospital, Qingdao, China
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2
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Zhang L, Wang C, Zhang C, Zhang L, Yang C, Zhang X. Investigating the landscape of immune-related genes and immunophenotypes in atherosclerosis: A bioinformatics Mendelian randomization study. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167649. [PMID: 39740383 DOI: 10.1016/j.bbadis.2024.167649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 12/11/2024] [Accepted: 12/27/2024] [Indexed: 01/02/2025]
Abstract
BACKGROUND Atherosclerosis, a leading cause of cardiovascular disease, is characterized by intricate interactions among lipid metabolism, inflammation, and immune response. Investigating immune-related genetic factors and immune cell infiltration in atherosclerotic tissues may provide insights into potential therapeutic targets. METHODS We analyzed transcriptomic data from atherosclerotic and normal tissues to identify differentially expressed genes (DEGs). Functional enrichment was performed using KEGG and GO pathway analyses, and immune-related DEGs were identified by intersecting DEGs with immune-related gene sets. Mendelian randomization (MR) was utilized to examine the causal relationship between immune-related DEGs and atherosclerosis. Immune cell infiltration was evaluated using Cibersort, MCP-counter, and xCell. Again, MR was performed to assess the causal effects of 731 immunophenotypes on atherosclerosis. RESULTS A total of 428 DEGs were identified between atherosclerotic and normal tissues, of which 112 were immune-related. Immune cell infiltration analysis highlighted significant differences, particularly in CD8 T cells and B cells. MR analysis demonstrated a significant causal relationship between HLA-DR on dendritic cells (OR [95%CI] =1.04[1.02-1.06], p = 1.03e-5) and coronary atherosclerosis. Furthermore, HLA-DR on myeloid dendritic cells (OR [95%CI] =1.12[1.07-1.17], p = 3.13e-06) and CD8 on CD8+ T cells (OR [95%CI] =1.12[1.05-1.18], p = 2.00e-04) were causally linked to atherosclerosis (excluding cerebral, coronary, and PAD). CONCLUSION Our findings highlight the crucial involvement of immune-related DEGs and specific immune cell types in the development of atherosclerosis. These results suggest that targeting immune pathways, particularly HLA DR on dendritic cells and CD8 on CD8+ T cells, may offer promising therapeutic strategies for atherosclerosis.
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Affiliation(s)
- Li Zhang
- Health Management Center, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
| | - Chaochao Wang
- Department of Emergency Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Ce Zhang
- Department of Emergency Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Liyun Zhang
- Health Management Center, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Chunmei Yang
- Health Management Center, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Xuefei Zhang
- Health Management Center, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
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Li Y, Ma Z, Li Y, Xiong T, Zhang Z, Kong B, Lu W, Zhao X, Zheng R, Tang Y, Yao P, Su Z, Wu Y, Xiong J. Cross-sectional and longitudinal associations between serum vitamin D and continuous metabolic syndrome score among children and adolescents: roles of levels of inflammation in peripheral blood. Nutr Metab (Lond) 2025; 22:2. [PMID: 39825325 PMCID: PMC11742777 DOI: 10.1186/s12986-024-00893-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 12/28/2024] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND Serum vitamin D deficiency is intricately linked to metabolic disorders, however, evidence on its association with continuous metabolic risk in children and adolescents remains insufficient. This study aims to elucidate the relationship between serum vitamin D levels and continuous metabolic risk. METHODS The cross-sectional analysis involved 4490 participants aged 6 ~ 18, and the longitudinal investigation included 1398 individuals aged 6 ~ 12 years. Serum 25(OH)D concentrations were quantified using liquid chromatography-mass spectrometry. Continuous Metabolic syndrome risk score (CMSRS), incorporating waist, blood pressure, blood lipid levels, and glucose metabolism as four components, utilizes age- and gender-specific Z scores to evaluate metabolic risk. Restricted cubic splines (RCS) were used to visualize dose-response relationships and generalized linear models (GLM) were used to estimate potential associations. Mediation analysis was used to evaluate the mediating role of levels of Neutrophil-to-lymphocyte ratio (NLR). RESULTS The RCS indicated a negative linear association between serum 25(OH)D levels and CMSRS (P-overall = 0.0066, P-nonlinear = 0.1393). GLM revealed that compared to Q1, with the quartiles of serum 25(OH)D concentrations increase, the β value ranged from 0.028 (95% CI: - 0.093, 0.037) to 0.001(95%CI: - 0.067, 0.069), and then to -0.074 (95%CI: -0.146, -0.003, P for trend = 0.0659). For every 10 ng/mL increase in serum 25(OH)D concentration corresponded to the β value change -0.058 (95%CI: -0.098, -0.017). This association was more pronounced in younger or overweight/obese individuals. Furthermore, in the longitudinal study, as the baseline quartile of serum 25(OH)D concentration increased, the estimated change of subsequent CMSRS indicated a decreasing trend, ranging from -0.085 (95%CI: -0.203, 0.032) to -0.166 (95%CI: - 0.285, - 0.046), and then to - 0.174 (95%CI: - 0.296, -0.053, P for trend = 0.0031). The mediating proportion of levels of NLR was 7.2%. CONCLUSIONS Higher serum 25(OH)D concentration is significantly associated with reduced CMSRS in children and adolescents, and adequate serum vitamin D levels play a prominent role in preventing long-term metabolic disorders, partly meditating by inflammation in peripheral blood.
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Affiliation(s)
- Yanyan Li
- Shenzhen Center for Chronic Disease Control, No. 2021 Buxin Road, Luohu District, Shenzhen, 518020, China
| | - Zhuang Ma
- Department of Nutrition and Food Hygiene, School of Public Health, Guangzhou Medical University, No. 1 Xinzao Road, Xinzao, Panyu District, Guangzhou, 511436, China
| | - Yan Li
- Shenzhen Center for Chronic Disease Control, No. 2021 Buxin Road, Luohu District, Shenzhen, 518020, China
| | - Ting Xiong
- Department of Nutrition and Food Hygiene, School of Public Health, Guangzhou Medical University, No. 1 Xinzao Road, Xinzao, Panyu District, Guangzhou, 511436, China
| | - Ziyang Zhang
- Shenzhen Center for Chronic Disease Control, No. 2021 Buxin Road, Luohu District, Shenzhen, 518020, China
| | - Bingxuan Kong
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education (MOE) Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Wenlong Lu
- Shenzhen Center for Chronic Disease Control, No. 2021 Buxin Road, Luohu District, Shenzhen, 518020, China
| | - Xiu Zhao
- Department of Endocrinology, Shenzhen Children's Hospital, No. 7019, Yitian Road, Futian District, Shenzhen, 518038, China
| | - Rongfei Zheng
- Department of Endocrinology, Shenzhen Children's Hospital, No. 7019, Yitian Road, Futian District, Shenzhen, 518038, China
| | - Yuhan Tang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education (MOE) Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Ping Yao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education (MOE) Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Zhe Su
- Department of Endocrinology, Shenzhen Children's Hospital, No. 7019, Yitian Road, Futian District, Shenzhen, 518038, China.
| | - Yuanjue Wu
- Department of Nutrition and Food Hygiene, School of Public Health, Guangzhou Medical University, No. 1 Xinzao Road, Xinzao, Panyu District, Guangzhou, 511436, China.
| | - Jingfan Xiong
- Shenzhen Center for Chronic Disease Control, No. 2021 Buxin Road, Luohu District, Shenzhen, 518020, China.
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Tsioulos G, Vallianou NG, Skourtis A, Dalamaga M, Kotsi E, Kargioti S, Adamidis N, Karampela I, Mourouzis I, Kounatidis D. Vaccination as a Promising Approach in Cardiovascular Risk Mitigation: Are We Ready to Embrace a Vaccine Strategy? Biomolecules 2024; 14:1637. [PMID: 39766344 PMCID: PMC11727084 DOI: 10.3390/biom14121637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/15/2024] [Accepted: 12/18/2024] [Indexed: 01/12/2025] Open
Abstract
Cardiovascular disease (CVD) remains a leading global health concern, with atherosclerosis being its principal cause. Standard CVD treatments primarily focus on mitigating cardiovascular (CV) risk factors through lifestyle changes and cholesterol-lowering therapies. As atherosclerosis is marked by chronic arterial inflammation, the innate and adaptive immune systems play vital roles in its progression, either exacerbating or alleviating disease development. This intricate interplay positions the immune system as a compelling therapeutic target. Consequently, immunomodulatory strategies have gained increasing attention, though none have yet reached widespread clinical adoption. Safety concerns, particularly the suppression of host immune defenses, remain a significant barrier to the clinical application of anti-inflammatory therapies. Recent decades have revealed the significant role of adaptive immune responses to plaque-associated autoantigens in atherogenesis, opening new perspectives for targeted immunological interventions. Preclinical models indicate that vaccines targeting specific atherosclerosis-related autoantigens can slow disease progression while preserving systemic immune function. In this context, numerous experimental studies have advanced the understanding of vaccine development by exploring diverse targeting pathways. Key strategies include passive immunization using naturally occurring immunoglobulin G (IgG) antibodies and active immunization targeting low-density lipoprotein cholesterol (LDL-C) and apolipoproteins, such as apolipoprotein B100 (ApoB100) and apolipoprotein CIII (ApoCIII). Other approaches involve vaccine formulations aimed at proteins that regulate lipoprotein metabolism, including proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesteryl ester transfer protein (CETP), and angiopoietin-like protein 3 (ANGPTL3). Furthermore, the literature highlights the potential for developing non-lipid-related vaccines, with key targets including heat shock proteins (HSPs), interleukins (ILs), angiotensin III (Ang III), and a disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS-7). However, translating these promising findings into safe and effective clinical therapies presents substantial challenges. This review provides a critical evaluation of current anti-atherosclerotic vaccination strategies, examines their proposed mechanisms of action, and discusses key challenges that need to be overcome to enable clinical translation.
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Affiliation(s)
- Georgios Tsioulos
- Fourth Department of Internal Medicine, Medical School, Attikon General University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Natalia G. Vallianou
- First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece; (S.K.); (N.A.)
| | - Alexandros Skourtis
- Department of Internal Medicine, Evangelismos General Hospital, 10676 Athens, Greece;
| | - Maria Dalamaga
- Department of Biological Chemistry, National and Kapodistrian University of Athens, 75 Mikras Asias Str., 11527 Athens, Greece;
| | - Evangelia Kotsi
- Second Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokratio General Hospital, 11527 Athens, Greece;
| | - Sofia Kargioti
- First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece; (S.K.); (N.A.)
| | - Nikolaos Adamidis
- First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece; (S.K.); (N.A.)
| | - Irene Karampela
- Second Department of Critical Care, Medical School, Attikon General University Hospital, University of Athens, 12461 Athens, Greece;
| | - Iordanis Mourouzis
- Department of Pharmacology, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Dimitris Kounatidis
- Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece;
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5
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Wu Y, Xu Y, Xu L. Pharmacological therapy targeting the immune response in atherosclerosis. Int Immunopharmacol 2024; 141:112974. [PMID: 39168023 DOI: 10.1016/j.intimp.2024.112974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 08/14/2024] [Accepted: 08/16/2024] [Indexed: 08/23/2024]
Abstract
Atherosclerosis (AS) is a chronic inflammatory disease characterized by the formation of atherosclerotic plaques that consist of numerous cells including smooth muscle cells, endothelial cells, immune cells, and foam cells. The most abundant innate and adaptive immune cells, including neutrophils, monocytes, macrophages, B cells, and T cells, play a pivotal role in the inflammatory response, lipoprotein metabolism, and foam cell formation to accelerate atherosclerotic plaque formation. In this review, we have discussed the underlying mechanisms of activated immune cells in promoting AS and reviewed published clinical trials for the treatment of AS by suppressing immune cell activation. We have also presented some crucial shortcomings of current clinical trials. Lastly, we have discussed the therapeutic potential of novel compounds, including herbal medicine and dietary food, in alleviating AS in animals. Despite these limitations, further clinical trials and experimental studies will enhance our understanding of the mechanisms modulated by immune cells and promote widespread drug use to treat AS by suppressing immune system-induced inflammation.
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Affiliation(s)
- Yirong Wu
- Department of Cardiology, Hangzhou First People's Hospital, 310006 Zhejiang, China
| | - Yizhou Xu
- Department of Cardiology, Hangzhou First People's Hospital, 310006 Zhejiang, China.
| | - Linhao Xu
- Department of Cardiology, Hangzhou First People's Hospital, 310006 Zhejiang, China; Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Translational Medicine Research Center, Hangzhou First People's Hospital, Hangzhou 310006, Zhejiang, China.
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6
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Zhao H, Jin Z, Li J, Fang J, Wu W, Fang JF. Novel insights of disulfidptosis-mediated immune microenvironment regulation in atherosclerosis based on bioinformatics analyses. Sci Rep 2024; 14:27336. [PMID: 39521794 PMCID: PMC11550432 DOI: 10.1038/s41598-024-78392-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024] Open
Abstract
Atherosclerosis (AS) is the leading cause of coronary heart disease, which is the primary cause of death worldwide. Recent studies have identified disulfidptosis as a new type of cell death that may be involved in onset and development of many diseases. However, the role of disulfidptosis in AS is not clear. In this study, bioinformatics analysis and experiments in vivo and in vitro were performed to evaluate the potential relationship between disulfidptosis and AS. AS-related sequencing data were obtained from the Gene Expression Omnibus (GEO). Bioinformatics techniques were used to evaluate differentially expressed genes (DEGs) associated with disulfidptosis-related AS. Hub genes were screened using least absolute shrinkage and selection operator (LASSO) and random forests (RF) methods. In addition, we established a foam cell model in vitro and an AS mouse model in vivo to verify the expressions of hub genes. In addition, we constructed a diagnostic nomogram with hub genes to predict progression of AS. Finally, the consensus clustering method was used to establish two different subtypes, and associations between subtypes and immunity were explored. As the results, 9 disulfidptosis-related AS DEGs were identified from GSE28829 and GSE43292 datasets. Evaluation of DEGs using LASSO and RF methods resulted in identification of 4 hub genes (CAPZB, DSTN, MYL6, PDLIM1), which were analyzed for diagnostic value using ROC curve analysis and verified in vitro and in vivo. Furthermore, a nomogram including hub genes was established that accurately predicted the occurrence of AS. The consensus clustering algorithm was used to separate patients with early atherosclerotic plaques and patients with advanced atherosclerotic plaques into two disulfidptosis subtypes. Cluster B displayed higher levels of infiltrating immune cells, which indicated that patients in cluster B may have a positive immune response for progression of AS. In summary, disulfidptosis-related genes including CAPZB, DSTN, MYL6, and PDLIM1 may be diagnostic markers and therapeutic targets for AS. In addition, these genes are closely related to immune cells, which may inform immunotherapy for AS.
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Affiliation(s)
- Huanyi Zhao
- First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China
| | - Zheng Jin
- First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China
| | - Junlong Li
- First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China
| | - Junfeng Fang
- First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China
| | - Wei Wu
- First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China.
| | - J F Fang
- First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China.
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7
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Chen T, Yang Y. Immunologic and inflammatory pathogenesis of chronic coronary syndromes: A review. Medicine (Baltimore) 2024; 103:e40354. [PMID: 39496055 PMCID: PMC11537619 DOI: 10.1097/md.0000000000040354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 10/15/2024] [Indexed: 11/06/2024] Open
Abstract
Chronic coronary syndrome (CCS) is a major cause of progression to acute coronary syndrome. Due to its insidious onset and complex etiology, this condition is often underestimated and insufficiently recognized, and traditional interventions for risk factors do not effectively control the disease progression. Current research suggests that immune and inflammatory pathways contribute to atherosclerosis and its clinical complications, thereby triggering the progression of CCS to acute coronary syndrome. This article primarily reviews the possible mechanisms of immune and inflammatory responses in CCS, with the aim of providing references for the diagnosis, treatment, and prevention of CCS.
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Affiliation(s)
- Tingting Chen
- Dali University School of Clinical Medicine, Yunnan, China
| | - Ying Yang
- Department of Cardiology, The First Affiliated Hospital of Dali University, Yunnan, China
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8
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Medina I, Wieland EB, Temmerman L, Otten JJT, Bermudez B, Bot I, Rademakers T, Wijnands E, Schurgers L, Mees B, van Berkel TJC, Goossens P, Biessen EAL. Colony stimulating factor 1 receptor (Csf1r) expressing cell ablation in mafia (macrophage-specific Fas-induced apoptosis) mice alters monocyte landscape and atherosclerotic lesion characteristics. Eur J Immunol 2024; 54:e2350943. [PMID: 39233527 DOI: 10.1002/eji.202350943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 07/29/2024] [Accepted: 07/30/2024] [Indexed: 09/06/2024]
Abstract
Macrophage infiltration and accumulation in the atherosclerotic lesion are associated with plaque progression and instability. Depletion of macrophages from the lesion might provide valuable insights into plaque stabilization processes. Therefore, we assessed the effects of systemic and local macrophage depletion on atherogenesis. To deplete monocytes/macrophages we used atherosclerosis-susceptible Apoe- /- mice, bearing a MaFIA (macrophage-Fas-induced-apoptosis) suicide construct under control of the Csf1r (CD115) promotor, where selective apoptosis of Csf1r-expressing cells was induced in a controlled manner, by administration of a drug, AP20187. Systemic induction of apoptosis resulted in a decrease in lesion macrophages and smooth-muscle cells. Plaque size and necrotic core size remained unaffected. Two weeks after the systemic depletion of macrophages, we observed a replenishment of the myeloid compartment. Myelopoiesis was modulated resulting in an expansion of CSF1Rlo myeloid cells in the circulation and a shift from Ly6chi monocytes toward Ly6cint and Ly6clo populations in the spleen. Local apoptosis induction led to a decrease in plaque burden and macrophage content with marginal effects on the circulating myeloid cells. Local, but not systemic depletion of Csf1r+ myeloid cells resulted in decreased plaque burden. Systemic depletion led to CSF1Rlo-monocyte expansion in blood, possibly explaining the lack of effects on plaque development.
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Affiliation(s)
- Indira Medina
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
- Division of Biopharmaceutics, Leiden Academic Center for Drug Research, Leiden, the Netherlands
| | - Elias B Wieland
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
| | - Lieve Temmerman
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
| | - Jeroen J T Otten
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
| | - Beatriz Bermudez
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
| | - Ilze Bot
- Division of Biopharmaceutics, Leiden Academic Center for Drug Research, Leiden, the Netherlands
| | - Timo Rademakers
- MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, the Netherlands
| | - Erwin Wijnands
- Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Leon Schurgers
- Department of Biochemistry, Maastricht University, Maastricht, the Netherlands
| | - Barend Mees
- Department of Vascular Surgery, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Theo J C van Berkel
- Division of Biopharmaceutics, Leiden Academic Center for Drug Research, Leiden, the Netherlands
| | - Pieter Goossens
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
| | - Erik A L Biessen
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Aachen, Germany
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9
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Padmanaban AM, Ganesan K, Ramkumar KM. A Co-Culture System for Studying Cellular Interactions in Vascular Disease. Bioengineering (Basel) 2024; 11:1090. [PMID: 39593750 PMCID: PMC11591305 DOI: 10.3390/bioengineering11111090] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 10/17/2024] [Accepted: 10/21/2024] [Indexed: 11/28/2024] Open
Abstract
Cardiovascular diseases (CVDs) are leading causes of morbidity and mortality globally, characterized by complications such as heart failure, atherosclerosis, and coronary artery disease. The vascular endothelium, forming the inner lining of blood vessels, plays a pivotal role in maintaining vascular homeostasis. The dysfunction of endothelial cells contributes significantly to the progression of CVDs, particularly through impaired cellular communication and paracrine signaling with other cell types, such as smooth muscle cells and macrophages. In recent years, co-culture systems have emerged as advanced in vitro models for investigating these interactions and mimicking the pathological environment of CVDs. This review provides an in-depth analysis of co-culture models that explore endothelial cell dysfunction and the role of cellular interactions in the development of vascular diseases. It summarizes recent advancements in multicellular co-culture models, their physiological and therapeutic relevance, and the insights they provide into the molecular mechanisms underlying CVDs. Additionally, we evaluate the advantages and limitations of these models, offering perspectives on how they can be utilized for the development of novel therapeutic strategies and drug testing in cardiovascular research.
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Affiliation(s)
- Abirami M. Padmanaban
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India;
| | - Kumar Ganesan
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong 999077, China;
| | - Kunka Mohanram Ramkumar
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India;
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10
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Kumari A, Pal A, Dada R. Effects of Yogic Practices Synchronized With Bandha and Kumbhaka on Biological and Psychological Factors of Aging in COVID-19-Recovered Patients: A Randomized Controlled Trial. Cureus 2024; 16:e71884. [PMID: 39559592 PMCID: PMC11573461 DOI: 10.7759/cureus.71884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/19/2024] [Indexed: 11/20/2024] Open
Abstract
Background and objectives Accelerated biological aging and age-associated diseases are strong risk factors for mortality and morbidity. Oxidative stress (OS) and anemia are possible pathophysiological causes of the various organ dysfunctions observed during COVID-19, decreasing health and life span. Ancient Yogic science seems to optimize all dimensions of human existence. As mentioned in ancient Yogic scriptures and documented in various studies, Yoga has been found to control accelerated biological aging and associated diseases. The study's objective was to authenticate and look into the effect of Yogic practices specifically synchronized with Kumbhaka and Bandha on markers of accelerated aging. Methods This randomized controlled trial was carried out in Mahendergarh city of Haryana on COVID-19-recovered adults aged between 30 and 60 years; 126 adults were randomized into two groups from Mahendergarh city: a control group (CG), 61 adults, and the experimental group (EG), 65 adults. During the final analysis, 56 adults in the experimental group received Yogic intervention for 120 days, and 61 adults remained the same in the control group during the intervention period. Consenting participants were randomized using computer-generated block randomization. The Yogic intervention was done 60 minutes/day five days a week for six months. Both groups' laboratory tests were carried out, which included malondialdehyde (MDA) level, total antioxidant capacity (TAC), glutathione (GSH) levels, hemoglobin (Hgb) level, body mass index (BMI), mental stress (perceived stress), and quality of life (QOL), which were estimated before and after the Yogic intervention. Results Yoga practice for 120 days (three mandals) in the experimental group has significantly reduced MDA level (p = 0.03) and perceived stress level (Perceived Stress Scale {PSS}) (p = 0.047), and BMI decreased in the Yoga group from 24.2 ± 4.8 to 23.6 ± 4.8, but no significant difference was observed in the values of BMI (p = 0.54). Improved antioxidant levels such as GSH level (p = 0.02), serum ferric-reducing antioxidant power (FRAP)/TAC activity (p = 0.04), and Hgb level (p = 0.02) were reported; with this, improved quality of life, World Health Organization Quality of Life (WHOQOL) Physical (p = 0.03), WHOQOL Psychological (p = 0.02), WHOQOL Social (p = 0.04), and WHOQOL Environment (p = 0.006), has been observed in the experimental group, whereas in the control group, we observed no significant difference in MDA level (p = 0.38), GSH level (p = 0.97), TAC level (p = 0.96), Hgb level (p = 1), BMI (p = 0.85), PSS (p = 0.83), and quality of life, WHOQOL Physical (p = 0.37), WHOQOL Psychological (p = 0.88), WHOQOL Social (p = 0.96), and WHOQOL Environment (p = 0.32). Conclusion These findings suggest that Yoga synchronized with Kumbhaka and Bandha may be a useful strategy for lowering oxidative stress and mental stress and improving antioxidant defense, hemoglobin level, and overall quality of life in COVID-19-recovered people, which might help reverse the biological decline of the human body and mind. The results of this study show that Yoga may break the link between old age and ill health. Hence, Yoga (with Bandha and Kumbhaka) may be the most reproducible way to extend the life span of humans, as mentioned in ancient Yogic scriptures.
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Affiliation(s)
- Anuj Kumari
- Yoga Sciences, Central University of Haryana, Mahendergarh, IND
| | - Ajay Pal
- Yoga Sciences, Central University of Haryana, Mahendergarh, IND
| | - Rima Dada
- Anatomy, Laboratory for Molecular Reproduction and Genetics, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
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Sharma H, Gupta N, Garg N, Dhankhar S, Chauhan S, Beniwal S, Saini D. Herbal Medicinal Nanoformulations for Psoriasis Treatment: Current State of Knowledge and Future Directions. THE NATURAL PRODUCTS JOURNAL 2024; 14. [DOI: 10.2174/0122103155273976231126141100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 10/14/2023] [Accepted: 10/23/2023] [Indexed: 12/01/2024]
Abstract
Background:Psoriasis is a persistent immune system disorder that influences the skin, leading to red, flaky patches that can be painful and irritated.Objective:Traditional treatments for psoriasis, such as topical creams and oral medications, may be effective but also have potential side effects. Herbal remedies have been used for centuries to treat skin conditions, and advancements in nanotechnology have led to the development of herbal nanoformulations that offer several advantages over traditional herbal remedies, such as efficacy, safety, and targeted delivery.Methods:The studies and reviews published under the title were looked up in several databases (including PubMed, Elsevier, and Google Scholar).Results:Several herbal nanoformulations, including those containing curcumin, aloe vera, and neem, have been shown to exhibit anti-inflammatory and immunomodulatory impacts, which will be useful within the treatment of psoriasis. However, more study is required to decide the efficacy and safety of these details, as well as the optimal dosing, duration of treatment, and potential side effects.Conclusion:Overall, herbal nanoformulations represent a promising area of research for the treatment of psoriasis, and may offer a safe and effective alternative or adjunct therapy to conventional treatments. This review article summarizes the present state of information for the herbal nanoformulations role in the treatment of psoriasis and their future perspectives.
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Affiliation(s)
- Himanshu Sharma
- Smt. Tarawati Institute of Bio-Medical and Applied Sciences, Roorkee, 247667, Dehradun, Uttarakhand, India
| | - Neha Gupta
- Smt. Tarawati Institute of Bio-Medical and Applied Sciences, Roorkee, 247667, Dehradun, Uttarakhand, India
| | - Nitika Garg
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India
| | - Sanchit Dhankhar
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India
| | - Samrat Chauhan
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India
| | - Suresh Beniwal
- Ganpati Institute of Pharmacy, Bilaspur, 135102, Yamuna Nagar, Haryana, India
| | - Deepak Saini
- Smt. Tarawati Institute of Bio-Medical and Applied Sciences, Roorkee, 247667, Dehradun, Uttarakhand, India
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Ma J, Wang X, Jia Y, Tan F, Yuan X, Du J. The roles of B cells in cardiovascular diseases. Mol Immunol 2024; 171:36-46. [PMID: 38763105 DOI: 10.1016/j.molimm.2024.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 04/30/2024] [Accepted: 05/04/2024] [Indexed: 05/21/2024]
Abstract
Damage to the heart can start the repair process and cause cardiac remodeling. B cells play an important role in this process. B cells are recruited to the injured place and activate cardiac remodeling through secreting antibodies and cytokines. Different types of B cells showed specific functions in the heart. Among all types of B cells, heart-associated B cells play a vital role in the heart by secreting TGFβ1. B cells participate in the activation of fibroblasts and promote cardiac fibrosis. Four subtypes of B cells in the heart revealed the relationship between the B cells' heterogeneity and cardiac remodeling. Many cardiovascular diseases like atherosclerosis, heart failure (HF), hypertension, myocardial infarction (MI), and dilated cardiomyopathy (DCM) are related to B cells. The primary mechanisms of these B cell-related activities will be discussed in this review, which may also suggest potential novel therapeutic targets.
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Affiliation(s)
- Jian Ma
- Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaotong Wang
- Department of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Yuewang Jia
- Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Fangyan Tan
- Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xin Yuan
- Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Jianlin Du
- Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Liu X, Zheng T, Zhang Y, Zhao Y, Liu F, Dai S, Zhang M, Zhang W, Zhang C, Zhang M, Li X. Endothelial Dickkopf-1 Promotes Smooth Muscle Cell-derived Foam Cell Formation via USP53-mediated Deubiquitination of SR-A During Atherosclerosis. Int J Biol Sci 2024; 20:2943-2964. [PMID: 38904030 PMCID: PMC11186357 DOI: 10.7150/ijbs.91957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 04/27/2024] [Indexed: 06/22/2024] Open
Abstract
Background: Shear stress-induced Dickkopf-1 (DKK1) secretion by endothelial cells (ECs) promotes EC dysfunction and accelerates atherosclerosis (AS). However, the paracrine role of endothelial DKK1 in modulating adjacent smooth muscle cells (SMCs) in atherosclerosis remains unclear. This study investigated the role of EC-secreted DKK1 in SMC-derived foam cell formation under shear stress, in vitro and in vivo. Methods: Parallel-plate co-culture flow system was used to explore the cellular communication between ECs and SMCs under shear stress in vitro. Endothelium-specific knockout of DKK1 (DKK1ECKO/APOE-/-) and endothelium-specific overexpression of DKK1 (DKK1ECTg) mice were constructed to investigate the role of endothelial DKK1 in atherosclerosis and SMC-derived foam cell formation in vivo. RNA sequencing (RNA-seq) was used to identify the downstream targets of DKK1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot, coimmunoprecipitation (Co-IP) assays and chromatin immunoprecipitation (ChIP) experiments were conducted to explore the underlying regulatory mechanisms. Results: DKK1 is transcriptionally upregulated in ECs under conditions of low shear stress, but not in co-cultured SMCs. However, DKK1 protein in co-cultured SMCs is increased via uptake of low shear stress-induced endothelial DKK1, thereby promoting lipid uptake and foam cell formation in co-cultured SMCs via the post-translational upregulation of scavenger receptor-A (SR-A) verified in parallel-plate co-culture flow system, DKK1ECKO and DKK1ECTg mice. RNA sequencing revealed that DKK1-induced SR-A upregulation in SMCs is dependent on Ubiquitin-specific Protease 53 (USP53), which bound to SR-A via its USP domain and cysteine at position 41, exerting deubiquitination to maintain the stability of the SR-A protein by removing the K48 ubiquitin chain and preventing proteasomal pathway degradation, thereby mediating the effect of DKK1 on lipid uptake in SMCs. Moreover, DKK1 regulates the transcription of USP53 by facilitating the binding of transcription factor CREB to the USP53 promoter. SMC-specific overexpression of USP53 via adeno-associated virus serotype 2 vectors in DKK1ECKO/APOE-/- mice reversed the alleviation of atherosclerotic plaque burden, SR-A expression and lipid accumulation in SMCs within plaques resulting from DKK1 deficiency. Conclusions: Our findings demonstrate that, endothelial DKK1, induced by pathological low shear stress, acts as an intercellular mediator, promoted the foam cell formation of SMCs. These results suggest that targeted intervention with endothelial DKK1 may confer beneficial effects on atherosclerosis.
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Affiliation(s)
- Xiaolin Liu
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Tengfei Zheng
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Yu Zhang
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Yachao Zhao
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Fengming Liu
- Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Shen Dai
- Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Meng Zhang
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Wencheng Zhang
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Cheng Zhang
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Mei Zhang
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Xiao Li
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
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You H, Han W. Identification of necroptosis-related diagnostic biomarkers in coronary heart disease. Heliyon 2024; 10:e30269. [PMID: 38726127 PMCID: PMC11079106 DOI: 10.1016/j.heliyon.2024.e30269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 04/12/2024] [Accepted: 04/23/2024] [Indexed: 05/12/2024] Open
Abstract
Background The implication of necroptosis in cardiovascular disease was already recognized. However, the molecular mechanism of necroptosis has not been extensively studied in coronary heart disease (CHD). Methods The differentially expressed genes (DEGs) between CHD and control samples were acquired in the GSE20681 dataset downloaded from the GEO database. Key necroptosis-related DEGs were captured and ascertained by bioinformatics analysis techniques, including weighted gene co-expression network analysis (WGCNA) and two machine learning algorithms, while single-gene gene set enrichment analysis (GSEA) revealed their molecular mechanisms. The diagnostic biomarkers were selected via receiver operating characteristic (ROC) analysis. Moreover, an analysis of immune elements infiltration degree was carried out. Authentication of pivotal gene expression at the mRNA level was investigated in vitro utilizing quantitative real-time PCR (qRT-PCR). Results A total of 94 DE-NRGs were recognized here, among which, FAM166B, NEFL, POLDIP3, PRSS37, and ZNF594 were authenticated as necroptosis-related biomarkers, and the linear regression model based on them presented an acceptable ability to different sample types. Following regulatory analysis, the ascertained biomarkers were markedly abundant in functions pertinent to blood circulation, calcium ion homeostasis, and the MAPK/cAMP/Ras signaling pathway. Single-sample GSEA exhibited that APC co-stimulation and CCR were more abundant, and aDCs and B cells were relatively scarce in CHD patients. Consistent findings from bioinformatics and qRT-PCR analyses confirmed the upregulation of NEFL and the downregulation of FAM166B, POLDIP3, and PRSS37 in CHD. Conclusion Our current investigation identified 5 necroptosis-related genes that could be diagnostic markers for CHD and brought a novel comprehension of the latent molecular mechanisms of necroptosis in CHD.
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Affiliation(s)
- Hongjun You
- Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, China
| | - Wenqi Han
- Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, China
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Li G, Cheng J, Yang L, Chen P, Duan X. Ethanol extract of Rubia yunnanensis inhibits carotid atherosclerosis via the PI3K/AKT signaling pathway. Biomed Rep 2024; 20:19. [PMID: 38170026 PMCID: PMC10758924 DOI: 10.3892/br.2023.1707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Accepted: 11/13/2023] [Indexed: 01/05/2024] Open
Abstract
Atherosclerosis is a multifactorial vascular disease caused by endothelial dysfunction. Because of adverse reactions to drugs used to treat atherosclerosis. For example, statins, which significantly reduce the burden of atherosclerotic disease, have been associated with muscle toxicity. There is a need to identify novel drugs for the prevention and treatment of atherosclerosis Rubia yunnanensis is a herbs commonly used in Asian countries for its protective effects against cardiovascular diseases. However, the mechanism of action of R. yunnanensis extract in carotid artery atherosclerosis has not been found. The carotid artery is usually used as a site for clinical evaluation of atherosclerosis. The present study aimed to determine the mechanism of action of R. yunnanensis extract in the inhibition of carotid atherosclerosis in apolipoprotein E gene knockout (ApoE-/-) mice. The mechanism of atherosclerosis inhibition was elucidated by detecting the blood lipid level, carotid artery pathology, and the protein expression of PI3K and AKT. The present study demonstrated that ethanol extract of R. yunnanensis reduced lipid levels, intima damage and carotid lipid accumulation and increased p-PI3K/PI3K and p-AKT/AKT protein levels in ApoE-/- mice fed high-fat diet for 12 weeks. It was hypothesized that the effects of R. yunnanensis extract may be achieved by regulation of the phosphatidylinositol-3-kinase/protein kinase B signaling pathway. Ethanol extract of R. yunnanensis decreased carotid atherosclerosis in ApoE-/- mice fed a high-fat diet via the phosphatidylinositol-3-kinase/protein kinase B signaling pathway. Therefore, R. yunnanensis may be a promising option for treating atherosclerosis in the future.
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Affiliation(s)
- Gaoyizhou Li
- Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, P.R. China
| | - Jianghao Cheng
- Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, P.R. China
| | - Liping Yang
- Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, P.R. China
| | - Pu Chen
- Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, P.R. China
| | - Xiaohua Duan
- Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, P.R. China
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Chen YH, Lin JA, Chen JR, Chen YL, Yang SC. Regular nutrition consultations reduced risk factors for cardiovascular diseases in adults. Nutrition 2024; 118:112259. [PMID: 38016253 DOI: 10.1016/j.nut.2023.112259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 09/25/2023] [Accepted: 10/01/2023] [Indexed: 11/30/2023]
Abstract
OBJECTIVES This study investigated the effects of regular nutrition consultations on reducing risk factors, including body mass index, body composition, blood pressure, blood lipid profile, blood glucose-related markers, and inflammatory factors for cardiovascular diseases. METHODS Data were collected from participants (n = 129) who completed eight dietary consultations and were divided into two groups according to the regularity of the consultations: an irregular group (with irregular consultation intervals; n = 39) and a regular group (accepted consultation once every 3 wk; n = 90). RESULTS Compared with the irregular group, the regular group had more significant reductions in cardiovascular disease risk factors, such as body mass index, body fat, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and insulin levels. Moreover, participants with a body mass index ≥ 27 kg/m2 presented significantly obvious improvements in cardiovascular risk factors, such as body weight; body mass index; visceral fat weight; and triglyceride, total cholesterol, low-density lipoprotein cholesterol, glycated hemoglobin, and insulin levels. CONCLUSION There is a proven benefit to regular nutrition consultation for adults with risk factors of cardiovascular diseases, particularly those who are obese.
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Affiliation(s)
- Yi-Hsiu Chen
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan
| | - Jung-An Lin
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan
| | - Jiun-Rong Chen
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan
| | - Ya-Ling Chen
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan; Research Center of Geriatric Nutrition, College of Nutrition, Taipei Medical University, Taipei, Taiwan
| | - Suh-Ching Yang
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan; Research Center of Geriatric Nutrition, College of Nutrition, Taipei Medical University, Taipei, Taiwan; Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan; School of Gerontology and Long-Term Care, College of Nursing, Taipei Medical University, Taipei, Taiwan.
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Wołoszyn-Durkiewicz A, Iwaszkiewicz-Grześ D, Świętoń D, Kujawa MJ, Jankowska A, Durawa A, Glasner P, Trzonkowski P, Glasner L, Szurowska E, Myśliwiec M. The Complex Network of Cytokines and Chemokines in Pediatric Patients with Long-Standing Type 1 Diabetes. Int J Mol Sci 2024; 25:1565. [PMID: 38338843 PMCID: PMC10855710 DOI: 10.3390/ijms25031565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/14/2024] [Accepted: 01/19/2024] [Indexed: 02/12/2024] Open
Abstract
Type 1 diabetes (T1D) is a progressive disorder leading to the development of microangiopathies and macroangiopathies. Numerous cytokines and chemokines are involved in the pathogenesis of T1D complications. The study aimed to assess the presence of complications in patients with long-standing T1D and its relationship with serum biomarker concentrations. We examined 52 T1D subjects, with a disease duration ≥4 years and 39 healthy controls. The group of T1D patients was further divided into subgroups based on the duration of the disease (<7 years and ≥7 years) and the metabolic control assessed by the HbAlc level (<8% and ≥8%). We used Luminex Technology to assess a wide range of biomarker concentrations. A 24 h urine test was done to evaluate the rate of albuminuria. Optical coherence tomography (OCT) was conducted to detect early retinopathic changes. Subclinical atherosclerosis was assessed by measuring the carotid intima-media thickness (IMT). T1D patients showed remarkably higher concentrations of EGF, eotaxin/CCL11, MDC/CCL22, sCD40L, TGF-α, and TNF-α. Moreover, we reported statistically significant correlations between cytokines and IMT. Biomarker concentrations depend on numerous factors such as disease duration, metabolic control, and the presence of complications. Although the majority of pediatric T1D patients do not present signs of overt complications, it is indispensable to conduct the screening for angiopathies already in childhood, as its early recognition may attenuate the further progression of complications.
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Affiliation(s)
- Anna Wołoszyn-Durkiewicz
- Department of Pediatrics, Diabetology and Endocrinology, Medical University of Gdańsk, 80-211 Gdańsk, Poland;
| | - Dorota Iwaszkiewicz-Grześ
- Department of Medical Immunology, Medical University of Gdańsk, 80-211 Gdańsk, Poland; (D.I.-G.); (P.T.)
| | - Dominik Świętoń
- 2nd Department of Radiology, Medical University of Gdańsk, 80-211 Gdańsk, Poland; (D.Ś.); (A.J.); (A.D.); (E.S.)
| | - Mariusz J. Kujawa
- 2nd Department of Radiology, Medical University of Gdańsk, 80-211 Gdańsk, Poland; (D.Ś.); (A.J.); (A.D.); (E.S.)
| | - Anna Jankowska
- 2nd Department of Radiology, Medical University of Gdańsk, 80-211 Gdańsk, Poland; (D.Ś.); (A.J.); (A.D.); (E.S.)
| | - Agata Durawa
- 2nd Department of Radiology, Medical University of Gdańsk, 80-211 Gdańsk, Poland; (D.Ś.); (A.J.); (A.D.); (E.S.)
| | - Paulina Glasner
- Department of Ophthalmology, Medical University of Gdańsk, 80-214 Gdańsk, Poland; (P.G.); (L.G.)
- Department of Anesthesiology and Intensive Care, Medical University of Gdańsk, 80-214 Gdańsk, Poland
| | - Piotr Trzonkowski
- Department of Medical Immunology, Medical University of Gdańsk, 80-211 Gdańsk, Poland; (D.I.-G.); (P.T.)
| | - Leopold Glasner
- Department of Ophthalmology, Medical University of Gdańsk, 80-214 Gdańsk, Poland; (P.G.); (L.G.)
| | - Edyta Szurowska
- 2nd Department of Radiology, Medical University of Gdańsk, 80-211 Gdańsk, Poland; (D.Ś.); (A.J.); (A.D.); (E.S.)
| | - Małgorzata Myśliwiec
- Department of Pediatrics, Diabetology and Endocrinology, Medical University of Gdańsk, 80-211 Gdańsk, Poland;
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Zhang YJ, Huang C, Zu XG, Liu JM, Li YJ. Use of Machine Learning for the Identification and Validation of Immunogenic Cell Death Biomarkers and Immunophenotypes in Coronary Artery Disease. J Inflamm Res 2024; 17:223-249. [PMID: 38229693 PMCID: PMC10790656 DOI: 10.2147/jir.s439315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 12/28/2023] [Indexed: 01/18/2024] Open
Abstract
Objective Immunogenic cell death (ICD) is part of the immune system's response to coronary artery disease (CAD). In this study, we bioinformatically evaluated the diagnostic and therapeutic utility of immunogenic cell death-related genes (IRGs) and their relationship with immune infiltration features in CAD. Methods We acquired the CAD-related datasets GSE12288, GSE71226, and GSE120521 from the Gene Expression Omnibus (GEO) database and the IRGs from the GeneCards database. After identifying the immune cell death-related differentially expressed genes (IRDEGs), we developed a risk model and detected immune subtypes in CAD. IRDEGs were identified using least absolute shrinkage and selection operator (LASSO) analysis. Using a nomogram, we confirmed that both the LASSO model and ICD signature genes had good diagnostic performance. Results There was a high degree of coincidence and immune representativeness between two CAD groups based on characteristic genes and hub genes. Hub genes were associated with the interaction of neuroactive ligands with receptors and cell adhesion receptors. The two groups differed in terms of adipogenesis, allograft rejection, and apoptosis, as well as the ICD signature and hub gene expression levels. The two CAD-ICD subtypes differed in terms of immune infiltration. Conclusion Quantitative real-time PCR (qRT-PCR) correlated CAD with the expression of OAS3, ITGAV, and PIBF1. The ICD signature genes are candidate biomarkers and reference standards for immune grouping in CAD and can be beneficial in precise immune-targeted therapy.
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Affiliation(s)
- Yan-jiao Zhang
- Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China
| | - Chao Huang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, People’s Republic of China
| | - Xiu-guang Zu
- Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China
| | - Jin-ming Liu
- Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China
| | - Yong-jun Li
- Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China
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Gerasimova EV, Shayakhmetova RU, Gerasimova DA, Popkova TV, Ananyeva LP. Systemic Sclerosis and Atherosclerosis: Potential Cellular Biomarkers and Mechanisms. Front Biosci (Schol Ed) 2023; 15:16. [PMID: 38163957 DOI: 10.31083/j.fbs1504016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 11/29/2023] [Accepted: 12/12/2023] [Indexed: 01/03/2024]
Abstract
Systemic sclerosis (SSc) is a rare systemic autoimmune disease of unknown etiology, which is characterized by endothelial dysfunction, pathologic vasculopathy, and increased tissue fibrosis. Traditionally, SSc has been regarded as a prototypical fibrotic disease in the family of systemic autoimmune diseases. Traditionally, emphasis has been placed on the three components of the pathogenesis of SSc: vascular, immune, and mesenchymal. Microvascular lesions, including endothelial dysfunction and smooth muscle cell migration into the intima of vessels in SSc, resemble the atherosclerotic process. Although microvascular disease is a hallmark of SSc, understanding the role of atherosclerotic vascular lesions in patients with SSc remains limited. It is still unknown whether the increased cardiovascular risk in SSc is related to specific cardiac complications (such as myocardial fibrosis) or the accelerated development of atherosclerosis. Different immune cell types appear to be involved in the immunopathogenesis of SSc via the activation of other immune cells, fibrosis, or vascular damage. Macrophages, B cells, T cells, dendritic cells, neutrophils, and endothelial cells have been reported to play the most important role in the pathogenesis of SSc and atherosclerosis. In our article, we reviewed the most significant and recent studies on the pathogenetic links between the development of SSc and the atherosclerotic process.
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Affiliation(s)
- Elena V Gerasimova
- Department of Systemic Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, 115522 Moscow, Russian Federation
| | - Rushana U Shayakhmetova
- Department of Systemic Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, 115522 Moscow, Russian Federation
| | - Daria A Gerasimova
- Department of Organization and Economics of Pharmacy, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119991 Moscow, Russian Federation
| | - Tatiana V Popkova
- Department of Systemic Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, 115522 Moscow, Russian Federation
| | - Lidia P Ananyeva
- Department of Systemic Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, 115522 Moscow, Russian Federation
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20
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Luciano N, Barone E, Timilsina S, Gershwin ME, Selmi C. Tumor Necrosis Factor Alpha Inhibitors and Cardiovascular Risk in Rheumatoid Arthritis. Clin Rev Allergy Immunol 2023; 65:403-419. [PMID: 38157095 DOI: 10.1007/s12016-023-08975-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/01/2023] [Indexed: 01/03/2024]
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by an increased risk of cardiovascular events, due to the complex interplay between traditional and disease-related risk factors. Chronic inflammation and persistent disease activity are the key determinants of this risk, but despite great improvement in the disease management and prognosis, cardiovascular events are still the main cause of morbidity and mortality in RA cohorts1. In the last decades, the advent of new biological and targeted-synthetic DMARDs was accompanied by an improvement in disease activity control, but the role of each class of drugs on CVD risk is still a matter a debate. Since their approval for RA treatment, tumor necrosis factor alpha (TNFα) inhibitors have been widely investigated to better understand their effects on cardiovascular outcomes. The hypothesis that the reduction of chronic inflammation with any treatment may reduce the cardiovascular risk has been recently confuted by the direct comparison of TNFα-inhibitors and JAK inhibitors in patients with RA and coexisting risk factors for cardiovascular disease. The aim of this literature review is to add to the available evidence to analyze the relationship between TNFα-inhibitors and CVD risk in patients with RA and also provide some clinical scenarios to better explain the treatment dilemmas. In particular, while data on major cardiovascular events and thromboembolism seem consistent with an inflammation-mediated benefit with TNFα-inhibitors, there remain concerns about the use of this class of bDMARDs in patients with chronic heart failure.
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Affiliation(s)
- Nicoletta Luciano
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Elisa Barone
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Suraj Timilsina
- Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, USA
| | - M Eric Gershwin
- Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, USA
| | - Carlo Selmi
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy.
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
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Fu J, Liang Y, Shi Y, Yu D, Wang Y, Chen P, Liu S, Lu F. HuangQi ChiFeng decoction maintains gut microbiota and bile acid homeostasis through FXR signaling to improve atherosclerosis. Heliyon 2023; 9:e21935. [PMID: 38034657 PMCID: PMC10685252 DOI: 10.1016/j.heliyon.2023.e21935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 10/31/2023] [Accepted: 10/31/2023] [Indexed: 12/02/2023] Open
Abstract
Huangqi Chifeng Decoction (HQCFT), a traditional Chinese medicine preparation, has long been used to treat cardiovascular and cerebrovascular diseases. However, the mechanism of the beneficial effect of HQCFT on atherosclerosis remains to be explored. In this work, to investigate the effects of HQCFT on bile acid (BA) metabolism and the gut microbiome in atherosclerosis, ApoE-/- mice were fed a with high-fat diet for 16 weeks to establish the AS model. HQCFT(1.95 g kg-1 and 3.9 g kg-1 per day) was administered intragastrically for 8 weeks to investigate the regulatory effects of HQCFT on gut microbiota and bile acid metabolism and to inhibit the occurrence and development of AS induced by a high-fat diet. Histopathology, liver function and blood lipids were used to assess whether HQCFT can reduce plaque area, regulate lipid levels and alleviate liver steatosis in AS mice. In addition, 16S rDNA sequencing was used to screen the gut microbiota structure, and ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS) was used to determine the bile acid profile. The mRNA and protein expression levels of bile acid metabolism were detected by RT‒PCR and WB to find the potential correlation. Results: HQCFT can regulate gut microbiota disorders, which was achieved by increasing gut microbiota diversity and altering Proteobacteria, Desulfobacterota, Deferribacteres, Rodentibacter, Parasutterella, and Mucispirillum interference abundance to improve AS-induced gut microbiota. HQCFT can also adjust the content of bile acids (TCA, LCA, DCA, TDCA, TLCA, UDCA, etc.), regulate bile acid metabolism, relieve liver fat accumulation, and inhibit the process of AS. In addition, HQCFT can restore the abnormal metabolism of bile acid caused by AS by regulating the expression of farnesoid X receptor (FXR), liver X receptor α (LXRα), ABCA1, ABCG1 and CYP7A1. Conclusion: HQCFT may play a part in the prevention of atherosclerosis by inhibiting the FXR/LXRα axis, increasing the expression of CYP7A1 in the liver, and regulating the interaction between the gut microbiota and bile acid metabolism.
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Affiliation(s)
- Jiaqi Fu
- Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Yuqin Liang
- Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Yunhe Shi
- Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Donghua Yu
- Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Yu Wang
- Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Pingping Chen
- Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Shumin Liu
- Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Fang Lu
- Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
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Yan F, Meng X, Cheng X, Pei W, Chen Y, Chen L, Zheng M, Shi L, Zhu C, Zhang X. Potential role between inflammatory cytokines and Tie-2 receptor levels and clinical symptoms in patients with first-episode schizophrenia. BMC Psychiatry 2023; 23:538. [PMID: 37491201 PMCID: PMC10367336 DOI: 10.1186/s12888-023-04913-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 05/29/2023] [Indexed: 07/27/2023] Open
Abstract
BACKGROUND Schizophrenia (SCZ) is associated with chronic low-grade inflammation, which may be involved in the underlying pathological mechanism of the disease and may influence patient prognosis. We evaluated the differences in serum cytokine and Tie-2 receptor levels between patients with first-episode SCZ and healthy controls and explored the correlation thereof with clinical symptoms. METHODS Seventy-six participants were recruited for the present study, including 40 patients with first-episode SCZ and 36 healthy controls. Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) scores, demographic data, and blood samples were collected at baseline. A hypersensitive Meso Scale Discovery (MSD) electrochemiluminescence assay system was used to measure cytokine and Tie-2 receptor levels. Spearman's correlation and stepwise linear regression were used to analyze the data. RESULTS Serum interleukin-1β and -4 levels were significantly increased, and Tie-2 levels were significantly decreased, in first-episode SCZ patients as compared to healthy controls. IL-1β levels were positively correlated with total BPRS scores, resistance subscores, and PANSS positive subscores. Furthermore, IL-1β levels were negatively correlated with Tie-2 receptor expression levels. Stepwise linear regression analysis demonstrated that IL-1β levels correlated positively with PANSS positive subscores and BPRS total scores. PANSS negative subscores, general psychopathology subscores, and PANSS total scores had positive effects on the Tie-2 receptor. Receiver operating characteristic (ROC) curve analysis showed that IL-1β and Tie-2 were highly sensitive and specific for predicting first-episode SCZ symptoms and achieving an area under the ROC curve of 0.8361 and 0.6462, respectively. CONCLUSION Our results showed that patients with first-episode SCZ have low-grade inflammation. IL-1β and Tie-2 receptors may be important mediators between inflammation and vascular dysfunction in patients with SCZ and may underlie the increased cardiovascular disease in this population. TRIAL REGISTRATION The clinical trial registration date was 06/11/2018, registration number was chiCTR1800019343.
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Affiliation(s)
- Fanfan Yan
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230022, China
- Anhui Clinical Center for Mental and Psychological Diseases, Hefei, 230022, China
- Hefei Fourth People's Hospital, Hefei, 230022, China
- Anhui Mental Health Center, Hefei, 230022, China
| | - Xiaojing Meng
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230022, China
- Anhui Clinical Center for Mental and Psychological Diseases, Hefei, 230022, China
- Hefei Fourth People's Hospital, Hefei, 230022, China
- Anhui Mental Health Center, Hefei, 230022, China
| | - Xialong Cheng
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230022, China
- Anhui Clinical Center for Mental and Psychological Diseases, Hefei, 230022, China
- Hefei Fourth People's Hospital, Hefei, 230022, China
- Anhui Mental Health Center, Hefei, 230022, China
| | - Wenzhi Pei
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230022, China
- Anhui Clinical Center for Mental and Psychological Diseases, Hefei, 230022, China
- Hefei Fourth People's Hospital, Hefei, 230022, China
- Anhui Mental Health Center, Hefei, 230022, China
| | - Yuanyuan Chen
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230022, China
| | - Long Chen
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230022, China
- Anhui Clinical Center for Mental and Psychological Diseases, Hefei, 230022, China
- Hefei Fourth People's Hospital, Hefei, 230022, China
- Anhui Mental Health Center, Hefei, 230022, China
| | - Mingming Zheng
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230022, China
- Anhui Clinical Center for Mental and Psychological Diseases, Hefei, 230022, China
- Hefei Fourth People's Hospital, Hefei, 230022, China
- Anhui Mental Health Center, Hefei, 230022, China
| | - Li Shi
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230022, China
| | - Cuizhen Zhu
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230022, China.
- Anhui Clinical Center for Mental and Psychological Diseases, Hefei, 230022, China.
- Hefei Fourth People's Hospital, Hefei, 230022, China.
- Anhui Mental Health Center, Hefei, 230022, China.
| | - Xulai Zhang
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230022, China.
- Anhui Clinical Center for Mental and Psychological Diseases, Hefei, 230022, China.
- Hefei Fourth People's Hospital, Hefei, 230022, China.
- Anhui Mental Health Center, Hefei, 230022, China.
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23
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Kantilafti M, Giannakou K, Chrysostomou S. Multimorbidity and food insecurity in adults: A systematic review and meta-analysis. PLoS One 2023; 18:e0288063. [PMID: 37410753 PMCID: PMC10325088 DOI: 10.1371/journal.pone.0288063] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 06/17/2023] [Indexed: 07/08/2023] Open
Abstract
Food insecurity is one of the main factors affecting multimorbidity. Previous studies have shown that food insecurity may lead to multimorbidity due to person's inability to consume nutritious diet. However, considering that multimorbidity may cause work-related disabilities and an unstable income, others support the possible effect that multimorbidity has on food insecurity. The purpose of this systematic review and meta-analysis is to examine the relationship between food insecurity and multimorbidity in adults. A systematic literature review of studies was performed using the PubMed, EBSCO and SCOPUS for all articles including adults ≥ 18-year-old with multimorbidity living in developed countries published from August 5th until December 7th 2022. Meta-analysis was performed considering results from the fully adjusted model. The methodological quality was assessed using the Newcastle-Ottawa Scale adapted for cross-sectional studies. This systematic review was not registered. This research received no specific grant from any funding agency. Four cross-sectional studies involving 45,404 participants were included in order to investigate the possible impact that food insecurity has on multimorbidity. The study findings showed an increased probability of multimorbidity 1.55 (95% CI:1.31-1.79, p<0.001, I2 = 44.1%) among people with food insecurity. Conversely, three of the included studies, involving 81,080 participants concluded that people with multimorbidity, have 2.58 (95% CI: 1.66-3.49, p<0.001, I2 = 89.7%) times higher odds to present food insecurity. This systematic review and meta-analysis provide evidence of a reverse association between food insecurity and multimorbidity. Further cross-sectional studies must be conducted in order to elucidate the association between multimorbidity and food insecurity across age groups and between the two genders.
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Affiliation(s)
- Maria Kantilafti
- Department of Health Sciences, School of Sciences, European University Cyprus, Nicosia, Cyprus
| | - Konstantinos Giannakou
- Department of Health Sciences, School of Sciences, European University Cyprus, Nicosia, Cyprus
| | - Stavri Chrysostomou
- Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia, Cyprus
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24
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Wu J, Li WH, Wang WR, Jin XQ, Liu EQ. Proteomics Analysis of Lipid Metabolism and Inflammatory Response in the Liver of Rabbits fed on a High Cholesterol Diet. Cell Biochem Biophys 2023:10.1007/s12013-023-01139-y. [PMID: 37160861 DOI: 10.1007/s12013-023-01139-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 04/16/2023] [Indexed: 05/11/2023]
Abstract
In this study, we aimed to analyze the proteomics of the liver in rabbits on a high cholesterol diet (HCD). We randomly divided New Zealand white rabbits into the normal diet group and the HCD group. We established the atherosclerosis model and measured plasma cholesterol and triglycerides. The model was successfully established using ultrasound examination and histopathological staining of the intima of aorta and liver of the two groups of rabbits. The differential proteins in the rabbit liver were analyzed using Tandem Mass Tags proteomic analysis technology. Finally, we used western blot to verify the reliability of proteomics. The results showed that compared with the control group, the serum lipid levels of rats in the HCD group was significantly increased, and the pathological sections showed the formation of atherosclerotic plaques in the aorta, inflammation, and adipose lesions in the liver. Proteomic analysis of the liver revealed 149 differences in HCD-expressed protein, which is mainly involved in inflammation and regulation of lipid and sugar metabolism. In addition, we verified differentially expressed liver proteins in the HCD group using western blot. We found that HCD caused lipid accumulation, abnormal glucose metabolism, and inflammatory response in the liver.
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Affiliation(s)
- Jing Wu
- Department of Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
- Department of Laboratory Animal Center, Ningxia Medical University, Yinchuan, 750001, China
| | - Wei-Hua Li
- Department of Laboratory Animal Center, Ningxia Medical University, Yinchuan, 750001, China
| | - Wei-Rong Wang
- Department of Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
- Department of Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China
| | - Xue-Qin Jin
- Department of Laboratory Animal Center, Ningxia Medical University, Yinchuan, 750001, China
| | - En-Qi Liu
- Department of Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
- Department of Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
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25
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Li Q, Mei A, Qian H, Min X, Yang H, Zhong J, Li C, Xu H, Chen J. The role of myeloid-derived immunosuppressive cells in cardiovascular disease. Int Immunopharmacol 2023; 117:109955. [PMID: 36878043 DOI: 10.1016/j.intimp.2023.109955] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 02/13/2023] [Accepted: 02/25/2023] [Indexed: 03/07/2023]
Abstract
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population found in the bone marrow, peripheral blood, and tumor tissue. Their role is mainly to inhibit the monitoring function of innate and adaptive immune cells, which leads to the escape of tumor cells and promotes tumor development and metastasis. Moreover, recent studies have found that MDSCs are therapeutic in several autoimmune disorders due to their strong immunosuppressive ability. Additionally, studies have found that MDSCs have an important role in the formation and progression of other cardiovascular diseases, such as atherosclerosis, acute coronary syndrome, and hypertension. In this review, we will discuss the role of MDSCs in the pathogenesis and treatment of cardiovascular disease.
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Affiliation(s)
- Qingmei Li
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China
| | - Aihua Mei
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China
| | - Hang Qian
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China
| | - Xinwen Min
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China
| | - Handong Yang
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China
| | - Jixin Zhong
- Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Chunlei Li
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China.
| | - Hao Xu
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China.
| | - Jun Chen
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China.
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Liu F, Huang Y, Liu F, Wang H. Identification of immune-related genes in diagnosing atherosclerosis with rheumatoid arthritis through bioinformatics analysis and machine learning. Front Immunol 2023; 14:1126647. [PMID: 36969166 PMCID: PMC10033585 DOI: 10.3389/fimmu.2023.1126647] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Accepted: 02/21/2023] [Indexed: 03/29/2023] Open
Abstract
Background Increasing evidence has proven that rheumatoid arthritis (RA) can aggravate atherosclerosis (AS), and we aimed to explore potential diagnostic genes for patients with AS and RA. Methods We obtained the data from public databases, including Gene Expression Omnibus (GEO) and STRING, and obtained the differentially expressed genes (DEGs) and module genes with Limma and weighted gene co-expression network analysis (WGCNA). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis, the protein-protein interaction (PPI) network, and machine learning algorithms [least absolute shrinkage and selection operator (LASSO) regression and random forest] were performed to explore the immune-related hub genes. We used a nomogram and receiver operating characteristic (ROC) curve to assess the diagnostic efficacy, which has been validated with GSE55235 and GSE73754. Finally, immune infiltration was developed in AS. Results The AS dataset included 5,322 DEGs, while there were 1,439 DEGs and 206 module genes in RA. The intersection of DEGs for AS and crucial genes for RA was 53, which were involved in immunity. After the PPI network and machine learning construction, six hub genes were used for the construction of a nomogram and for diagnostic efficacy assessment, which showed great diagnostic value (area under the curve from 0.723 to 1). Immune infiltration also revealed the disorder of immunocytes. Conclusion Six immune-related hub genes (NFIL3, EED, GRK2, MAP3K11, RMI1, and TPST1) were recognized, and the nomogram was developed for AS with RA diagnosis.
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Affiliation(s)
- Fuze Liu
- Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Yue Huang
- Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Fuhui Liu
- School of Clinical Medical, Weifang Medical University, Weifang, China
| | - Hai Wang
- Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Atzeni F, Maiani S, Corda M, Rodríguez-Carrio J. Diagnosis and management of cardiovascular risk in rheumatoid arthritis: main challenges and research agenda. Expert Rev Clin Immunol 2023; 19:279-292. [PMID: 36651086 DOI: 10.1080/1744666x.2023.2170351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
INTRODUCTION Rheumatoid arthritis (RA) exhibit a cardiovascular (CV) risk that is 1.5-2.0 times higher compared to the general population. This CV risk excess is likely caused by the involvement of chronic inflammation and immune dysregulation. Therefore, conventional algorithms and imaging techniques fail to fully account for this risk excess and provide a suboptimal risk stratification, hence limiting clinical management in this setting. AREAS COVERED Compelling evidence has suggested a role for adaptations of conventional algorithms (Framingham, SCORE, AHA, etc) or the development of RA-specific algorithms, as well as the use of a number of several, noninvasive imaging techniques to improve CV risk assessment in RA populations. Similarly, in-depth analyses of atherosclerosis pathogenesis in RA patients have shed new light into a plethora of soluble biomarkers (such as inflammatory cytokines, vascular remodeling mediators or autoantibodies) that may provide incremental value for CV risk stratification. EXPERT OPINION Extensive research has demonstrated a lack of performance of chart adaptations in capturing real CV risk in RA population, as well as for RA-specific algorithms. Similarly, limitations have been detected in the use of soluble mediators. The development of a novel, RA-specific algorithm including classical and non-traditional risk factors may be advisable.
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Affiliation(s)
- Fabiola Atzeni
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Messina, Italy
| | - Silvia Maiani
- Clinical Cardiology, Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
| | - Marco Corda
- S.C. Cardiologia UTIC, ARNAS, G.Brotzu, Cagliari, Italy
| | - Javier Rodríguez-Carrio
- Area of Immunology, Department of Functional Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.,Area of Metabolism, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
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Karpouzas GA, Papotti B, Ormseth SR, Palumbo M, Hernandez E, Marchi C, Zimetti F, Budoff MJ, Ronda N. Serum cholesterol loading capacity of macrophages is regulated by seropositivity and C-reactive protein in rheumatoid arthritis patients. Rheumatology (Oxford) 2023; 62:1254-1263. [PMID: 35809057 DOI: 10.1093/rheumatology/keac394] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 06/21/2022] [Accepted: 06/21/2022] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVE Excessive cholesterol accumulation in macrophages is the pivotal step underlying atherosclerotic plaque formation. We here explore factors in the serum of patients with RA, and mechanisms through which they interact with and influence cholesterol loading capacity (CLC) of macrophages. METHODS In a cross-sectional observational cohort of 104 patients with RA, CLC was measured as intracellular cholesterol content in human THP-1-derived macrophages after incubation with patient serum. Low-density lipoprotein (LDL) oxidation was measured in terms of oxidized phospholipids on apoB100-containing particles (oxPL-apoB100). Antibodies against oxidized LDL (anti-oxLDL), proprotein convertase subtilisin/Kexin type-9 (PCSK9) and high-sensitivity CRP were also quantified. All analyses adjusted for atherosclerotic cardiovascular disease (ASCVD) risk score, obesity, total LDL, statin use, age at diagnosis, and anti-oxLDL IgM. RESULTS OxPL-apoB100, anti-oxLDL IgG and PCSK9 were positively associated with CLC (all P < 0.020). OxPL-apoB100 directly influenced CLC only in dual RF- and ACPA-positive patients [unstandardized b (95% bootstrap CI)=2.08 (0.38, 3.79)]. An indirect effect of oxPL-apoB100 on CLC through anti-oxLDL IgG increased, along with level of CRP [index of moderated mediation = 0.55 (0.05-1.17)]. CRP also moderated yet another indirect effect of oxPL-apoB100 on CLC through upregulation of PCSK9, but only among dual-seropositive patients [conditional indirect effect = 0.64 (0.13-1.30)]. CONCLUSION Oxidized LDL can directly influence CLC in dual-seropositive RA patients. Two additional and independent pathways-via anti-oxLDL IgG and PCSK9-may mediate the effects of oxPL-apoB100 on CLC, depending on CRP and seropositivity status. If externally validated, these findings may have clinical implications for cardiovascular risk prevention.
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Affiliation(s)
- George A Karpouzas
- Division of Rheumatology, Harbor-UCLA Medical Center, The Lundquist Institute, Torrance, CA, USA
| | - Bianca Papotti
- Department of Food and Drug, University of Parma, Parma, Italy
| | - Sarah R Ormseth
- Division of Rheumatology, Harbor-UCLA Medical Center, The Lundquist Institute, Torrance, CA, USA
| | | | - Elizabeth Hernandez
- Division of Rheumatology, Harbor-UCLA Medical Center, The Lundquist Institute, Torrance, CA, USA
| | - Cinzia Marchi
- Department of Food and Drug, University of Parma, Parma, Italy
| | | | - Matthew J Budoff
- Division of Cardiology, Harbor-UCLA Medical Center and The Lundquist Institute, Torrance, CA, USA
| | - Nicoletta Ronda
- Department of Food and Drug, University of Parma, Parma, Italy
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Szydlak R. Mesenchymal stem cells in ischemic tissue regeneration. World J Stem Cells 2023; 15:16-30. [PMID: 36909782 PMCID: PMC9993139 DOI: 10.4252/wjsc.v15.i2.16] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/10/2022] [Accepted: 01/19/2023] [Indexed: 02/21/2023] Open
Abstract
Diseases caused by ischemia are one of the leading causes of death in the world. Current therapies for treating acute myocardial infarction, ischemic stroke, and critical limb ischemia do not complete recovery. Regenerative therapies opens new therapeutic strategy in the treatment of ischemic disorders. Mesenchymal stem cells (MSCs) are the most promising option in the field of cell-based therapies, due to their secretory and immunomodulatory abilities, that contribute to ease inflammation and promote the regeneration of damaged tissues. This review presents the current knowledge of the mechanisms of action of MSCs and their therapeutic effects in the treatment of ischemic diseases, described on the basis of data from in vitro experiments and preclinical animal studies, and also summarize the effects of using these cells in clinical trial settings. Since the obtained therapeutic benefits are not always satisfactory, approaches aimed at enhancing the effect of MSCs in regenerative therapies are presented at the end.
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Affiliation(s)
- Renata Szydlak
- Chair of Medical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kraków 31-034, Poland
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Interactions between Platelets and Tumor Microenvironment Components in Ovarian Cancer and Their Implications for Treatment and Clinical Outcomes. Cancers (Basel) 2023; 15:cancers15041282. [PMID: 36831623 PMCID: PMC9953912 DOI: 10.3390/cancers15041282] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/07/2023] [Accepted: 02/13/2023] [Indexed: 02/19/2023] Open
Abstract
Platelets, the primary operatives of hemostasis that contribute to blood coagulation and wound healing after blood vessel injury, are also involved in pathological conditions, including cancer. Malignancy-associated thrombosis is common in ovarian cancer patients and is associated with poor clinical outcomes. Platelets extravasate into the tumor microenvironment in ovarian cancer and interact with cancer cells and non-cancerous elements. Ovarian cancer cells also activate platelets. The communication between activated platelets, cancer cells, and the tumor microenvironment is via various platelet membrane proteins or mediators released through degranulation or the secretion of microvesicles from platelets. These interactions trigger signaling cascades in tumors that promote ovarian cancer progression, metastasis, and neoangiogenesis. This review discusses how interactions between platelets, cancer cells, cancer stem cells, stromal cells, and the extracellular matrix in the tumor microenvironment influence ovarian cancer progression. It also presents novel potential therapeutic approaches toward this gynecological cancer.
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31
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Meng Q, Liu H, Liu J, Pang Y, Liu Q. Advances in immunotherapy modalities for atherosclerosis. Front Pharmacol 2023; 13:1079185. [PMID: 36703734 PMCID: PMC9871313 DOI: 10.3389/fphar.2022.1079185] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 12/22/2022] [Indexed: 01/12/2023] Open
Abstract
Cardiovascular disease (CVD) is one of the leading causes of death worldwide. Atherosclerosis is the pathological basis of atherosclerotic cardiovascular disease (ASCVD). Atherosclerosis is now understood to be a long-term immune-mediated inflammatory condition brought on by a complicated chain of factors, including endothelial dysfunction, lipid deposits in the artery wall, and monocyte-derived macrophage infiltration, in which both innate immunity and adaptive immunity play an indispensable role. Recent studies have shown that atherosclerosis can be alleviated by inducing a protective immune response through certain auto-antigens or exogenous antigens. Some clinical trials have also demonstrated that atherosclerotic is associated with the presence of immune cells and immune factors in the body. Therefore, immunotherapy is expected to be a new preventive and curative measure for atherosclerosis. In this review, we provide a summary overview of recent progress in the research of immune mechanisms of atherosclerosis and targeted therapeutic pathways.
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Affiliation(s)
- Qingwen Meng
- Department of Pharmacy, The First Affiliated Hospital of Hainan Medical University, Haikou, China,Deparment of Cardiovascular, The First Affiliated Hospital of Hainan Medical University, Haikou, China,Hainan Provincial Key Laboratory of Tropical Brain Research and Transformation, Hainan Medical University, Haikou, China
| | - Huajiang Liu
- Deparment of Cardiovascular, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Jinteng Liu
- School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, China
| | - Yangyang Pang
- School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, China
| | - Qibing Liu
- Department of Pharmacy, The First Affiliated Hospital of Hainan Medical University, Haikou, China,School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, China,*Correspondence: Qibing Liu,
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32
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Zhang L, Tang C, Zhang M, Tong X, Xie Y, Yan R, Wang X, Zhang X, Liu D, Li S. Single cell meta-analysis of EndMT and EMT state in COVID-19. Front Immunol 2022; 13:976512. [PMID: 36248845 PMCID: PMC9558222 DOI: 10.3389/fimmu.2022.976512] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 08/24/2022] [Indexed: 11/13/2022] Open
Abstract
COVID-19 prognoses suggests that a proportion of patients develop fibrosis, but there is no evidence to indicate whether patients have progression of mesenchymal transition (MT) in the lungs. The role of MT during the COVID-19 pandemic remains poorly understood. Using single-cell RNA sequencing, we profiled the transcriptomes of cells from the lungs of healthy individuals (n = 45), COVID-19 patients (n = 58), and idiopathic pulmonary fibrosis (IPF) patients (n = 64) human lungs to map the entire MT change. This analysis enabled us to map all high-resolution matrix-producing cells and identify distinct subpopulations of endothelial cells (ECs) and epithelial cells as the primary cellular sources of MT clusters during COVID-19. For the first time, we have identied early and late subgroups of endothelial mesenchymal transition (EndMT) and epithelial-mesenchymal transition (EMT) using analysis of public databases for single-cell sequencing. We assessed epithelial subgroups by age, smoking status, and gender, and the data suggest that the proportional changes in EMT in COVID-19 are statistically significant. Further enumeration of early and late EMT suggests a correlation between invasive genes and COVID-19. Finally, EndMT is upregulated in COVID-19 patients and enriched for more inflammatory cytokines. Further, by classifying EndMT as early or late stages, we found that early EndMT was positively correlated with entry factors but this was not true for late EndMT. Exploring the MT state of may help to mitigate the fibrosis impact of SARS-CoV-2 infection.
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Affiliation(s)
- Lanlan Zhang
- Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, And Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China
- *Correspondence: Dan Liu, ; Lanlan Zhang, ; Xin Zhang,
| | - Chuang Tang
- Department of Gastroenterology, West China (Airport) Hospital, Sichuan University, Chengdu, China
| | - Min Zhang
- Oncology Bussiness Department, Novogene Co., Ltd, Beijing, China
| | - Xia Tong
- Department of Gastroenterology, West China (Airport) Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China
| | - Yingying Xie
- Department of Nephrology, Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, China
| | | | - Xiangjun Wang
- First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xin Zhang
- Department of Gastroenterology, West China (Airport) Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China
- *Correspondence: Dan Liu, ; Lanlan Zhang, ; Xin Zhang,
| | - Dan Liu
- Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, And Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China
- *Correspondence: Dan Liu, ; Lanlan Zhang, ; Xin Zhang,
| | - Shasha Li
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, United States
- Harvard Medical School, Boston, MA, United States
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Bu Y, Peng M, Tang X, Xu X, Wu Y, Chen AF, Yang X. Protective effects of metformin in various cardiovascular diseases: Clinical evidence and AMPK-dependent mechanisms. J Cell Mol Med 2022; 26:4886-4903. [PMID: 36052760 PMCID: PMC9549498 DOI: 10.1111/jcmm.17519] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 07/22/2022] [Accepted: 07/29/2022] [Indexed: 11/29/2022] Open
Abstract
Metformin, a well-known AMPK agonist, has been widely used as the first-line drug for treating type 2 diabetes. There had been a significant concern regarding the use of metformin in people with cardiovascular diseases (CVDs) due to its potential lactic acidosis side effect. Currently growing clinical and preclinical evidence indicates that metformin can lower the incidence of cardiovascular events in diabetic patients or even non-diabetic patients beyond its hypoglycaemic effects. The underlying mechanisms of cardiovascular benefits of metformin largely involve the cellular energy sensor, AMPK, of which activation corrects endothelial dysfunction, reduces oxidative stress and improves inflammatory response. In this minireview, we summarized the clinical evidence of metformin benefits in several widely studied cardiovascular diseases, such as atherosclerosis, ischaemic/reperfusion injury and arrhythmia, both in patients with or without diabetes. Meanwhile, we highlighted the potential AMPK-dependent mechanisms in in vitro and/or in vivo models.
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Affiliation(s)
- Yizhi Bu
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China
| | - Mei Peng
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China
| | - Xinyi Tang
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China
| | - Xu Xu
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China
| | - Yifeng Wu
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China
| | - Alex F Chen
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China.,Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaoping Yang
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China
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Extracellular Vesicles, Inflammation, and Cardiovascular Disease. Cells 2022; 11:cells11142229. [PMID: 35883672 PMCID: PMC9320258 DOI: 10.3390/cells11142229] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 07/11/2022] [Accepted: 07/12/2022] [Indexed: 12/15/2022] Open
Abstract
Cardiovascular disease is a leading cause of death worldwide. The underlying mechanisms of most cardiovascular disorders involve innate and adaptive immune responses, and extracellular vesicles are implicated in both. In this review, we describe the mechanistic role of extracellular vesicles at the intersection of inflammatory processes and cardiovascular disease. Our discussion focuses on atherosclerosis, myocardial ischemia and ischemic heart disease, heart failure, aortic aneurysms, and valvular pathology.
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Alnuqaydan AM, Almutary A, Bhat GR, Mir TA, Wani SI, Rather MY, Mir SA, Alshehri B, Alnasser S, Ali Zainy FM, Rah B. Evaluation of the Cytotoxic, Anti-Inflammatory, and Immunomodulatory Effects of Withaferin A (WA) against Lipopolysaccharide (LPS)-Induced Inflammation in Immune Cells Derived from BALB/c Mice. Pharmaceutics 2022; 14:pharmaceutics14061256. [PMID: 35745829 PMCID: PMC9229769 DOI: 10.3390/pharmaceutics14061256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Revised: 06/08/2022] [Accepted: 06/09/2022] [Indexed: 12/25/2022] Open
Abstract
(1) Background: Inflammation is one of the primary responses of the immune system and plays a key role in the pathophysiology of various diseases. Recent reports suggest that various phytochemicals exhibit promising anti-inflammatory and immunomodulation activities with relatively few undesirable effects, thus offering a viable option to deal with inflammation and associated diseases. The current study evaluates the anti-inflammatory and immunomodulatory effects of withaferin A (WA) in immune cells extracted from BALB/c mice. (2) Methods: MTT assays were performed to assess the cell viability of splenocytes and anti-inflammatory doses of WA. Under aseptic conditions, the isolation of macrophages and splenocytes from BALB/c mice was performed to investigate the anti-inflammatory effects of WA. Analysis of the expression of proinflammatory cytokines and associated signaling mediators was performed using proinflammatory assay kits, real-time polymerase chain reaction (RT-PCR), and immunoblotting, while the quantification of B and T cells was performed by flow cytometry. (3) Results: Our results demonstrated that WA exhibits anti-inflammatory and immunomodulatory effects in LPS-stimulated macrophages and splenocytes derived from BALB/c mice, respectively. Mechanistically, we found that WA promotes an anti-inflammatory effect on LPS-stimulated macrophages by attenuating the secretion and expression of proinflammatory cytokines TNF-α, IL-1β, IL-6, and the inflammation modulator NO, both at the transcriptional and translational level, respectively. Further, WA inhibits LPS-stimulated inflammatory signaling by dephosphorylation of p-Akt-Ser473 and p-ERK1/2. This dephosphorylation does not allow IĸB-kinase activation to disrupt IĸB–NF-ĸB interaction. The consistent interaction of IĸB with NF-ĸB in WA-treated cells attenuates the activation of downstream inflammatory signaling mediators Cox-2 and iNOS expression, which play crucial roles in inflammatory signaling. Additionally, we observed significant immunomodulation of LPS-stimulated spleen-derived lymphocytes by suppression of B (CD19) and T (CD4+/CD8+) cell populations after treatment with WA. (4) Conclusion: WA exhibits anti-inflammatory and immunomodulatory activity by modulating Akt/ERK/NF-kB-mediated inflammatory signaling in macrophages and immunosuppression of B (CD19) and T cell (CD4+/CD8+) populations in splenocytes after LPS stimulation. These results suggest that WA could act as a potential anti-inflammatory/immunomodulatory molecule and support its use in the field of immunopharmacology to modulate immune system cells.
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Affiliation(s)
- Abdullah M. Alnuqaydan
- Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi Arabia; (A.M.A.); (A.A.)
| | - Abdulmajeed Almutary
- Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi Arabia; (A.M.A.); (A.A.)
| | - Gh Rasool Bhat
- Advanced Centre for Human Genetics, Sher-i-Kashmir Institute of Medical Sciences, Srinagar 190011, Jammu and Kashmir, India; (G.R.B.); (S.I.W.)
| | - Tanveer Ahmad Mir
- Laboratory of Tissue/Organ Bioengineering & BioMEMS, Organ Transplant Centre of Excellence, Transplantation Research & Innovation (Dpt)-R, King Faisal Specialist Hospital and Research Centre, MBC 03, Riyadh 11211, Saudi Arabia;
| | - Shadil Ibrahim Wani
- Advanced Centre for Human Genetics, Sher-i-Kashmir Institute of Medical Sciences, Srinagar 190011, Jammu and Kashmir, India; (G.R.B.); (S.I.W.)
| | - Mohd Younis Rather
- Multidisplinary Research Unit, Government Medical College, Srinagar 190010, Jammu and Kashmir, India;
| | - Shabir Ahmad Mir
- Department of Medical Laboratory Sciences, College of Applied Medical Science, Majmaah University, Al Majmaah 11952, Saudi Arabia; (S.A.M.); (B.A.)
| | - Bader Alshehri
- Department of Medical Laboratory Sciences, College of Applied Medical Science, Majmaah University, Al Majmaah 11952, Saudi Arabia; (S.A.M.); (B.A.)
| | - Sulaiman Alnasser
- Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Buraidah 51452, Saudi Arabia;
| | - Faten M. Ali Zainy
- Chemistry Department, Faculty of Science, University of Jeddah, Jeddah 21589, Saudi Arabia;
| | - Bilal Rah
- Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi Arabia; (A.M.A.); (A.A.)
- Advanced Centre for Human Genetics, Sher-i-Kashmir Institute of Medical Sciences, Srinagar 190011, Jammu and Kashmir, India; (G.R.B.); (S.I.W.)
- Correspondence: or or
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Thirty-Five-Year History of Desialylated Lipoproteins Discovered by Vladimir Tertov. Biomedicines 2022; 10:biomedicines10051174. [PMID: 35625910 PMCID: PMC9138341 DOI: 10.3390/biomedicines10051174] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 05/17/2022] [Accepted: 05/17/2022] [Indexed: 12/11/2022] Open
Abstract
Atherosclerosis is one of the leading causes of death in developed and developing countries. The atherogenicity phenomenon cannot be separated from the role of modified low-density lipoproteins (LDL) in atherosclerosis development. Among the multiple modifications of LDL, desialylation deserves to be discussed separately, since its atherogenic effects and contribution to atherogenicity are often underestimated or, simply, forgotten. Vladimir Tertov is linked to the origin of the research related to desialylated lipoproteins, including the association of modified LDL with atherogenicity, autoimmune nature of atherosclerosis, and discovery of sialidase activity in blood plasma. The review will briefly discuss all the above-mentioned information, with a description of the current situation in the research.
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Yin Y, Xie Z, Chen D, Guo H, Han M, Zhu Z, Bi J. Integrated investigation of DNA methylation, gene expression and immune cell population revealed immune cell infiltration associated with atherosclerotic plaque formation. BMC Med Genomics 2022; 15:108. [PMID: 35534881 PMCID: PMC9082837 DOI: 10.1186/s12920-022-01259-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 05/03/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND The clinical consequences of atherosclerosis are significant source of morbidity and mortality throughout the world, while the molecular mechanisms of the pathogenesis of atherosclerosis are largely unknown. METHODS In this study, we integrated the DNA methylation and gene expression data in atherosclerotic plaque samples to decipher the underlying association between epigenetic and transcriptional regulation. Immune cell classification was performed on the basis of the expression pattern of detected genes. Finally, we selected ten genes with dysregulated methylation and expression levels for RT-qPCR validation. RESULTS Global DNA methylation profile showed obvious changes between normal aortic and atherosclerotic lesion tissues. We found that differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were highly associated with atherosclerosis by being enriched in atherosclerotic plaque formation-related pathways, including cell adhesion and extracellular matrix organization. Immune cell fraction analysis revealed that a large number of immune cells, especially macrophages, activated mast cells, NK cells, and Tfh cells, were specifically enriched in the plaque. DEGs associated with immune cell fraction change showed that they were mainly related to the level of macrophages, monocytes, resting NK cells, activated CD4 memory T cells, and gamma delta T cells. These genes were highly enriched in multiple pathways of atherosclerotic plaque formation, including blood vessel remodeling, collagen fiber organization, cell adhesion, collagen catalogic process, extractable matrix assembly, and platelet activation. We also validated the expression alteration of ten genes associated with infiltrating immune cells in atherosclerosis. CONCLUSIONS In conclusion, these findings provide new evidence for understanding the mechanisms of atherosclerotic plaque formation, and provide a new and valuable research direction based on immune cell infiltration.
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Affiliation(s)
- Yihong Yin
- Department of Neural Medicine, The Second Hospital of Shandong University, Shandong University, No. 247 Beiyuan Street, Jinan, 250033, China
- Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 17 Lujiang Road, Hefei, 230001, China
| | - Zhaohong Xie
- Department of Neural Medicine, The Second Hospital of Shandong University, Shandong University, No. 247 Beiyuan Street, Jinan, 250033, China
| | - Dong Chen
- Center for Genome Analysis, Wuhan Ruixing Biotechnology Co. Ltd, Wuhan, 430075, China
| | - Hao Guo
- Center for Genome Analysis, Wuhan Ruixing Biotechnology Co. Ltd, Wuhan, 430075, China
| | - Min Han
- Department of Neural Medicine, The Second Hospital of Shandong University, Shandong University, No. 247 Beiyuan Street, Jinan, 250033, China
| | - Zhengyu Zhu
- Department of Neural Medicine, The Second Hospital of Shandong University, Shandong University, No. 247 Beiyuan Street, Jinan, 250033, China.
| | - Jianzhong Bi
- Department of Neural Medicine, The Second Hospital of Shandong University, Shandong University, No. 247 Beiyuan Street, Jinan, 250033, China.
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Zhang HM, Li XY, Lin N, Niu YX, Gu HX, Lu S, Yang Z, Qin L, Su Q. Lymphocytes ≥ 2.9 (10 9/L) in Newly Diagnosed Diabetes Are A Predictor of Future CVD Events. Curr Med Sci 2022; 42:327-332. [PMID: 35290604 DOI: 10.1007/s11596-022-2541-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 08/28/2021] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Atherosclerosis is considered a chronic inflammatory condition. The immune system is a key mediator in the initiation and progression of atherosclerosis. In a previous study, we found that the immune system was activated in diabetes and that total white blood cell (WBC) counts were elevated significantly in diabetic patients. To investigate whether WBC subtype counts in newly diagnosed diabetes are risk factors for future cardiovascular disease (CVD) events, we conducted a prospective population-based cohort study. METHODS A total of 1498 newly diagnosed diabetic patients aged 40 to 70 years old were followed up for three years. Participants with previous CVD history and abnormal WBC counts were excluded. CVD events were recorded during follow-up. RESULTS We found that the baseline lymphocyte counts were independently associated with cardiovascular events during follow-up, with the Exp (β) (95% CI) at 1.749 (1.084-2.821). Lymphocyte count ≥2.9 (109/L) was significantly associated with the development of CVD (HR, 2.29; 95% CI, 1.12-4.67). The corresponding incidence of CVD per 1000 person-year for the lymphocyte count ≤2.8 (109/L) and lymphocyte count ≥2.9 (109/L) groups were 11.26 and 26.38, respectively. CONCLUSION We concluded that even in a normal range, higher lymphocyte levels may result in a significantly higher CVD risk among diabetic patients. Lymphocyte count ≥2.9 (109/L) is an independent predictor of developing future CVD events.
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Affiliation(s)
- Hong-Mei Zhang
- Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China
| | - Xiao-Yong Li
- Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China
| | - Ning Lin
- Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China
| | - Yi-Xin Niu
- Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China
| | - Hong-Xia Gu
- Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University (Chongming Branch), Shanghai, 202150, China
| | - Shuai Lu
- Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University (Chongming Branch), Shanghai, 202150, China
| | - Zhen Yang
- Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China
| | - Li Qin
- Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China. .,Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University (Chongming Branch), Shanghai, 202150, China.
| | - Qing Su
- Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China.
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Karpouzas GA, Ormseth SR, Ronda N, Hernandez E, Budoff MJ. Lipoprotein oxidation may underlie the paradoxical association of low cholesterol with coronary atherosclerotic risk in rheumatoid arthritis. J Autoimmun 2022; 129:102815. [PMID: 35366608 DOI: 10.1016/j.jaut.2022.102815] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 03/09/2022] [Accepted: 03/10/2022] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To compare coronary plaque burden, proatherogenic cytokines, oxidized low-density lipoprotein (oxLDL), anti-oxLDL antibodies, lipoprotein(a)-cholesterol, and their relationships in patients with rheumatoid arthritis with low-density lipoprotein cholesterol (LDL-C)<1.8 mmol/L versus ≥1.8 mmol/L. Also, to study differences in inflammation and proprotein convertase subtilisin/kexin type-9 (PCSK9), which impacts LDL clearance, in patients with low versus high LDL-C. METHODS Computed tomography angiography evaluated coronary plaque (noncalcified, partially calcified, fully calcified, and high-risk plaque) in 150 patients from a single-center observational cohort. Ox-LDL, anti-oxLDL IgG, lipoprotein(a)-cholesterol, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6, tumor necrosis factor-α (TNF-α) and PCSK9 were measured. Analyses adjusted for Framingham general cardiovascular risk score, statin use, and high-density lipoprotein cholesterol. RESULTS Patients with LDL-C<1.8 mmol/L versus ≥1.8 mmol/L demonstrated: 1) higher likelihood of per-segment plaque (adjusted-OR = 1.67 [95%CI = 1.10-2.55], p = 0.017) and high-risk plaque presence (adjusted-OR 2.78 [95%CI = 1.06-7.29], p = 0.038); 2) greater anti-oxLDL titers (p = 0.020), which positively associated with TNF-α and likelihood of noncalcified, partially calcified and high-risk plaque presence only in patients with LDL-C<1.8 mmol/L (all p-for-interaction≤0.046); 3) increased lipoprotein(a)-cholesterol content (10.33% [8.11-12.54] versus 6.68% [6.10-7.25], p < 0.001), which positively associated with oxLDL (p < 0.001) and anti-oxLDL (p = 0.036); 4) higher interleukin-6 and PCSK9. No differences in CRP, ESR, or oxLDL were observed. CONCLUSION RA patients with LDL-C<1.8 mmol/L had more coronary plaque, higher anti-oxLDL titers and anti-oxLDL associated with plaque only in this group. It is possible the observed paradoxical association of low LDL-C with greater atherosclerosis may be related to higher production of the oxidation-prone lipoprotein(a)-cholesterol and anti-oxLDL antibodies, resulting in increased vascular LDL uptake and plaque formation.
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Affiliation(s)
- George A Karpouzas
- Division of Rheumatology, Harbor-UCLA Medical Center and Lundquist Institute for Biomedical Innovation, Torrance, CA, USA.
| | - Sarah R Ormseth
- Division of Rheumatology, Harbor-UCLA Medical Center and Lundquist Institute for Biomedical Innovation, Torrance, CA, USA
| | - Nicoletta Ronda
- Department of Food and Drug, University of Parma, Parco Area Delle Scienze 27/A, 43124, Parma, Italy
| | - Elizabeth Hernandez
- Division of Rheumatology, Harbor-UCLA Medical Center and Lundquist Institute for Biomedical Innovation, Torrance, CA, USA
| | - Matthew J Budoff
- Division of Cardiology, Harbor-UCLA Medical Center and Lundquist Institute for Biomedical Innovation, Torrance, CA, USA
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41
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Vissenaekens H, Grootaert C, Raes K, De Munck J, Smagghe G, Boon N, Van Camp J. Quercetin Mitigates Endothelial Activation in a Novel Intestinal-Endothelial-Monocyte/Macrophage Coculture Setup. Inflammation 2022; 45:1600-1611. [PMID: 35352237 DOI: 10.1007/s10753-022-01645-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 01/16/2022] [Accepted: 02/03/2022] [Indexed: 11/30/2022]
Abstract
Atherosclerosis initiation is associated with a pro-inflammatory state of the endothelium. Quercetin is a flavonoid abundantly present in plant-based foods, with a possible impact on cardiovascular health. In this study, the effects of quercetin on lipopolysaccharide (LPS)-mediated endothelial inflammation and monocyte adhesion and migration, which are initial steps of the atherogenic process, are studied. Novel in vitro multicellular models simulating the intestinal-endothelial-monocytes/macrophages axis allowed to combine relevant intestinal flavonoid absorption, metabolism and efflux, and the consequent bioactivity towards peripheral endothelial cells. In this triple coculture, quercetin exposure decreased monocyte adhesion to and macrophage migration through an LPS-stressed endothelium, and this was associated with significantly lower levels of soluble vascular cell adhesion molecule-1 (sVCAM-1). Furthermore, quercetin decreased the pro-inflammatory cell environment upon LPS-induced endothelial activation, in terms of tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and sVCAM-1 expression. These findings highlight a mode-of-action by which quercetin may positively impact the initial states of atherosclerosis under more physiologically relevant conditions in terms of quercetin concentrations, metabolites, and intercellular crosstalk.
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Affiliation(s)
- Hanne Vissenaekens
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000, Ghent, Belgium.,Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, 9000, Ghent, Belgium
| | - Charlotte Grootaert
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000, Ghent, Belgium
| | - Katleen Raes
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000, Ghent, Belgium
| | - Julie De Munck
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000, Ghent, Belgium
| | - Guy Smagghe
- Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, 9000, Ghent, Belgium
| | - Nico Boon
- Center for Microbial Ecology and Technology (CMET), Faculty of Bioscience Engineering, Ghent University, 9000, Ghent, Belgium
| | - John Van Camp
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000, Ghent, Belgium.
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42
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Atherosclerosis severity in patients with familial hypercholesterolemia: The role of T and B lymphocytes. ATHEROSCLEROSIS PLUS 2022; 48:27-36. [PMID: 36644561 PMCID: PMC9833267 DOI: 10.1016/j.athplu.2022.03.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 03/11/2022] [Accepted: 03/15/2022] [Indexed: 02/01/2023]
Abstract
Background and aims Familial hypercholesterolemia (FH) is characterized by lifelong exposure to high LDL-c concentrations and premature atherosclerotic cardiovascular disease; nevertheless, disease severity can be heterogeneous.We aimed at evaluating if the immune-inflammatory system could modulate atherosclerosis burden in FH. Methods From a cohort of subjects with confirmed FH (Dutch Lipid Clinic Network and genotype), 92 patients receiving high-intensity lipid-lowering therapy (statin ± ezetimibe) were included. The extension and severity of coronary atherosclerosis was assessed by standardized reporting systems (CAD-RADS) for coronary computed tomography angiography (CCTA) and coronary artery calcium (CAC) scores. Lipids, apolipoproteins, anti-oxLDL and anti-apolipoprotein B-D peptide (anti-ApoB-D) autoantibodies (IgM and IgG), lymphocytes subtypes, platelet, monocyte and endothelial microparticles (MP), IgM levels (circulating or produced by B1 cells) and cytokines in the supernatant of cultured cells were determined. Multiple linear regression models evaluated associations of these biomarkers with CAC and CAD-RADS scores. Results In univariate analysis CAC correlated with age, systolic blood pressure, TCD4+ cells, and titers of IgM anti-ApoB-D. In multiple linear regression [ANOVA F = 2.976; p = 0.024; R2 = 0.082), CD4+T lymphocytes (B = 35.289; beta = 0.277; p = 0.010; 95%CI for B 8.727 to 61.851), was independently associated with CAC. CAD-RADS correlated with age, systolic blood pressure, titers of IgM anti-ApoB-D, and endothelial MP in univariate analysis. In multiple linear regression, [ANOVA F = 2.790; p = 0.032; R2 = 0.119), only age (B = 0.027; beta = 0.234; p = 0.049; 95% CI for B 0.000 to 0.053) was independent predictor. Conclusions In subjects with FH, under high-intensity lipid-lowering therapy, age and CD4+T cells were associated to atherosclerosis burden.
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43
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Kurmanbekova BT, Noruizbaeva AM. Cardiovascular Effects of Metformin. RATIONAL PHARMACOTHERAPY IN CARDIOLOGY 2022. [DOI: 10.20996/1819-6446-2022-02-12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Type 2 diabetes mellitus is one of the most important independent risk factors for the development, progression and mortality from cardiovascular diseases (CVD). The world communities are faced with the question of developing the optimal management tactics for such comorbidity patients. Thus, the prescribed drug should not only have an adequate hypoglycemic effect, but also have a number of cardioprotective properties, be safe in patients with CVD, and possibly even improve the prognosis and reduce mortality rates. This review is devoted to a representative of the biguanide class - metformin, which is one of the earliest and most effective antihyperglycemic drugs, both as monotherapy and in combination with other antihyperglycemic drugs and insulin; while the evidence base for its cardiovascular profile is only gaining momentum. Thus, the purpose of this review is to highlight the cardiovascular effects of metformin in the context of recent research.
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Affiliation(s)
- B. T. Kurmanbekova
- National Center of cardiology and internal medicine named after academician M.Mirrakhimov
| | - A. M. Noruizbaeva
- National Center of cardiology and internal medicine named after academician M.Mirrakhimov
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44
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Bernabe-Ortiz A, Carrillo-Larco RM, Gilman RH, Smeeth L, Checkley W, Miranda JJ. High-sensitivity C-reactive protein and all-cause mortality in four diverse populations: The CRONICAS Cohort Study. Ann Epidemiol 2022; 67:13-18. [PMID: 34923118 PMCID: PMC8960343 DOI: 10.1016/j.annepidem.2021.12.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 12/06/2021] [Accepted: 12/12/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE To assess the association between all-cause mortality and hs-CRP, based mainly on the cumulative burden approach. METHODS Cohort study with adults ≥35 years from general population, using hs-CRP at two timepoints: at baseline and 30 months later to establish different exposures: change over time, cumulative, and weighted cumulative hs-CRP. The outcome was all-cause mortality assessed 7 years later. Cox models were generated to quantify the association. RESULTS Data from 3,119 participants (mean age 55.6 years, and 51.2% females), were analyzed. During follow-up, 164 (5.6%) deaths occurred over 20,314.5 person-years, indicating an overall mortality rate of 8.1 per 1,000 person-years. In multivariable model, hs-CRP at baseline was associated with high risk of mortality (HR = 1.77; 95%CI: 1.28-2.46). Similarly, hs-CRP change over time (HR = 2.50; 95%CI: 1.46-4.29), as well as cumulative and weighted cumulative hs-CRP (HR = 2.05; 95%CI: 1.31-3.20) were associated with greater risk of all-cause mortality. The weighted cumulative hs-CRP had the best goodness-of-fit for mortality prediction. CONCLUSIONS In this cohort across diverse geographical low-resource settings, high levels of hs-CRP were strongly associated with all-cause mortality. Two measurements of hs-CRP are better than one to predict mortality, and the weighted cumulative approach had the best prognostic fit.
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Affiliation(s)
- Antonio Bernabe-Ortiz
- CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru.
| | - Rodrigo M. Carrillo-Larco
- CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru.,Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Robert H. Gilman
- CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru.,Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
| | - Liam Smeeth
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - William Checkley
- CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru.,Division of Pulmonary and Critical Care, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - J. Jaime Miranda
- CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru.,Department of Medicine, School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru
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45
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Belce A, Ozkan BN, Dumlu FS, Sisman BH, Guler EM. Evaluation of Oxidative Stress and Inflammatory Biomarkers Pre and Post-Treatment in New Diagnosed Atherosclerotic Patients. Clin Exp Hypertens 2022; 44:320-325. [PMID: 35172655 DOI: 10.1080/10641963.2022.2036993] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Atherosclerosis is a chronic vascular inflammatory disease associated to oxidative stress and endothelial dysfunction. It is characterized by lipid accumulation in the arterial wall, increased hyperlipidemia, oxidative stress, lipid peroxidation, and protein oxidation. Our study included 45 patients ages of 40-60 and 45 healthy volunteers with similar demographic characteristics without any chronic disease as well. Fasting plasma glucose, BUN, creatinine, LDL-cholesterol, HDL-cholesterol, triglyceride, total cholesterol, HbA1c, and C-reactive protein (CRP) levels were measured using commercial kits by autoanalyzer. The oxidative stress biomarkers total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), native thiol (NT), catalase (CAT), paraoxonase (PON1), and arylesterase (ARES) enzyme activities were measured using photometric methods. The inflammatory biomarkers interleukin 1 beta (IL-1β), tumor necrosis factor-α (TNF-α), presepsin (PSPN), and raftlin (RFTN1) levels were measured with ELISA Kits. Oxidative stress index (OSI) and disulfide (DIS) were calculated. The clinical, biochemical biomarkers such as BUN, creatinine, HDL, LDL, total cholesterol, triglyceride, and CRP levels were found to be higher than the control group and lower post-treatment compared to the pre-treatment group (p <0.001). The oxidative stress parameters, TOS, OSI, and DIS levels were found to be higher than the control group, and the levels before the treatment were statistically significantly higher than after the treatment (p < 0.001). Antioxidant biomarkers TAS, TT, and NT levels were low in the patient group. Inflammatory biomarkers were highest before treatment and decreased with treatment. Oxidative stress and inflammation, which increased in atherosclerosis patients may guide disease prognosis and treatment strategies.
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Affiliation(s)
- Ahmet Belce
- Department of Medical Biochemistry, Biruni University, Faculty of Medicine, Zeytinburnu, Istanbul
| | - Beyza Nur Ozkan
- Department of Medical Biochemistry, University of Health Science Turkey, Hamidiye Faculty of Medicine, Uskudar, Istanbul
| | - Fatma Sena Dumlu
- Department of Medical Biochemistry, University of Health Science Turkey, Hamidiye Faculty of Medicine, Uskudar, Istanbul
| | - Behice Hande Sisman
- Department of Cardiology, Bezmialem Vakıf University, Faculty of Medicine, Fatih, Istanbul
| | - Eray Metin Guler
- Department of Medical Biochemistry, University of Health Sciences Turkey, Haydarpasa Numune Health Application and Research Center, Uskudar, Istanbul
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46
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Exosomes in cardiovascular diseases: a blessing or a sin for the mankind. Mol Cell Biochem 2022; 477:833-847. [PMID: 35064412 DOI: 10.1007/s11010-021-04328-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 12/07/2021] [Indexed: 12/13/2022]
Abstract
Cardiovascular diseases (CVDs) comprises disorders of blood vessels and heart. Multiple cells in the heart suggests that hetero-cellular communication, which is an important aspect in heart functioning and there is a need to elucidate the way in which this inter-cellular communication occurs. Now a days, exosomal research has gained much attention. Exosomes, nano-shuttles, are EVs with diameters ranging from 40 to 160 nm (average 100 nm), secreted by body cells. These vesicles act as cell-to-cell communicators and are carriers of important biomolecules such as RNAs, miRNAs, Proteins and lipids. Exosomes can change the gene expression of the recipient cells, thereby, changes the cellular characteristics. Exosomes have known to play an essential role in protection as well as progression of various cardiovascular diseases. In the present review, role of exosomes in various CVDs have been discussed.
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47
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Meng LB, Zhang YM, Luo Y, Gong T, Liu DP. Chronic Stress A Potential Suspect Zero of Atherosclerosis: A Systematic Review. Front Cardiovasc Med 2022; 8:738654. [PMID: 34988123 PMCID: PMC8720856 DOI: 10.3389/fcvm.2021.738654] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 11/29/2021] [Indexed: 12/11/2022] Open
Abstract
Atherosclerosis (AS) is a chronic vascular inflammatory disease, in which the lipid accumulation in the intima of the arteries shows yellow atheromatous appearance, which is the pathological basis of many diseases, such as coronary artery disease, peripheral artery disease and cerebrovascular disease. In recent years, it has become the main cause of death in the global aging society, which seriously endangers human health. As a result, research on AS is increasing. Lesions of atherosclerosis contain macrophages, T cells and other cells of the immune response, together with cholesterol that infiltrates from the blood. Recent studies have shown that chronic stress plays an important role in the occurrence and development of AS. From the etiology of disease, social, environmental and genetic factors jointly determine the occurrence of disease. Atherosclerotic cardio-cerebrovascular disease (ASCVD) is often caused by chronic stress (CS). If it cannot be effectively prevented, there will be biological changes in the body environment successively, and then the morphological changes of the corresponding organs. If the patient has a genetic predisposition and a combination of environmental factors triggers the pathogenesis, then chronic stress can eventually lead to AS. Therefore, this paper discusses the influence of chronic stress on AS in the aspects of inflammation, lipid metabolism, endothelial dysfunction, hemodynamics and blood pressure, plaque stability, autophagy, ferroptosis, and cholesterol efflux.
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Affiliation(s)
- Ling-Bing Meng
- Department of Cardiology, National Center of Gerontology, Institute of Geriatric Medicine, Beijing Hospital, Chinese Academy of Medical Sciences, Beijing, China.,Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Yuan-Meng Zhang
- Department of Internal Medicine, The Third Medical Centre of Chinese People's Liberation Army (PLA) General Hospital, The Training Site for Postgraduate of Jinzhou Medical University, Beijing, China
| | - Yue Luo
- Department of Respiratory, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Tao Gong
- Department of Neurology, National Center of Gerontology, National Center of Gerontology, Institute of Geriatric Medicine, Beijing Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - De-Ping Liu
- Department of Cardiology, National Center of Gerontology, Institute of Geriatric Medicine, Beijing Hospital, Chinese Academy of Medical Sciences, Beijing, China.,Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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48
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Sakic A, Chaabane C, Ambartsumian N, Klingelhöfer J, Lemeille S, Kwak BR, Grigorian M, Bochaton-Piallat ML. Neutralization of S100A4 induces stabilization of atherosclerotic plaques: role of smooth muscle cells. Cardiovasc Res 2022; 118:141-155. [PMID: 33135065 PMCID: PMC8752361 DOI: 10.1093/cvr/cvaa311] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 10/20/2020] [Indexed: 01/20/2023] Open
Abstract
AIMS During atherosclerosis, smooth muscle cells (SMCs) accumulate in the intima where they switch from a contractile to a synthetic phenotype. From porcine coronary artery, we isolated spindle-shaped (S) SMCs exhibiting features of the contractile phenotype and rhomboid (R) SMCs typical of the synthetic phenotype. S100A4 was identified as a marker of R-SMCs in vitro and intimal SMCs, in pig and man. S100A4 exhibits intra- and extracellular functions. In this study, we investigated the role of extracellular S100A4 in SMC phenotypic transition. METHODS AND RESULTS S-SMCs were treated with oligomeric recombinant S100A4 (oS100A4), which induced nuclear factor (NF)-κB activation. Treatment of S-SMCs with oS100A4 in combination with platelet-derived growth factor (PDGF)-BB induced a complete SMC transition towards a pro-inflammatory R-phenotype associated with NF-κB activation, through toll-like receptor-4. RNA sequencing of cells treated with oS100A4/PDGF-BB revealed a strong up-regulation of pro-inflammatory genes and enrichment of transcription factor binding sites essential for SMC phenotypic transition. In a mouse model of established atherosclerosis, neutralization of extracellular S100A4 decreased area of atherosclerotic lesions, necrotic core, and CD68 expression and increased α-smooth muscle actin and smooth muscle myosin heavy chain expression. CONCLUSION We suggest that the neutralization of extracellular S100A4 promotes the stabilization of atherosclerotic plaques. Extracellular S100A4 could be a new target to influence the evolution of atherosclerotic plaques.
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MESH Headings
- Actins/metabolism
- Animals
- Antibodies, Neutralizing/pharmacology
- Antigens, CD/metabolism
- Antigens, Differentiation, Myelomonocytic/metabolism
- Aorta/drug effects
- Aorta/metabolism
- Aorta/pathology
- Aortic Diseases/drug therapy
- Aortic Diseases/genetics
- Aortic Diseases/metabolism
- Aortic Diseases/pathology
- Atherosclerosis/drug therapy
- Atherosclerosis/genetics
- Atherosclerosis/metabolism
- Atherosclerosis/pathology
- Becaplermin/pharmacology
- Cells, Cultured
- Disease Models, Animal
- Humans
- Mice, Inbred C57BL
- Mice, Knockout, ApoE
- Muscle, Smooth, Vascular/drug effects
- Muscle, Smooth, Vascular/metabolism
- Muscle, Smooth, Vascular/pathology
- Myocytes, Smooth Muscle/drug effects
- Myocytes, Smooth Muscle/metabolism
- Myocytes, Smooth Muscle/pathology
- Myosin Heavy Chains/metabolism
- Phenotype
- Plaque, Atherosclerotic
- S100 Calcium-Binding Protein A4/antagonists & inhibitors
- S100 Calcium-Binding Protein A4/metabolism
- S100 Calcium-Binding Protein A4/pharmacology
- Signal Transduction
- Smooth Muscle Myosins/metabolism
- Sus scrofa
- Toll-Like Receptor 4/metabolism
- Mice
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Affiliation(s)
- Antonija Sakic
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Chiraz Chaabane
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Noona Ambartsumian
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
| | - Jörg Klingelhöfer
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
| | - Sylvain Lemeille
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Brenda R Kwak
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Mariam Grigorian
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
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49
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Williams PT. Quantile-Specific Heritability of Inflammatory and Oxidative Stress Biomarkers Linked to Cardiovascular Disease. J Inflamm Res 2022; 15:85-103. [PMID: 35023945 PMCID: PMC8743501 DOI: 10.2147/jir.s347402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 12/16/2021] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Heritability (h2 , the proportion of the phenotypic variance attributable to additive genetic effects) is traditionally assumed to be constant throughout the distribution of the phenotype. However, the heritabilities of circulating C-reactive protein, interleukin-6, plasminogen activator inhibitor type-1 (PAI-1), and monocyte chemoattractant protein-1 (MCP-1) concentrations depend upon whether the phenotype is high or low relative to their distributions (quantile-dependent expressivity), which may account for apparent gene-environment interactions. Whether the heritabilities of other inflammatory biomarkers linked to cardiovascular disease are quantile-dependent remain to be determined. PATIENTS AND METHODS Quantile-specific offspring-parent (βOP) and full-sib regression slopes (βFS) were estimated by applying quantile regression to the age- and sex-adjusted phenotypes of families surveyed as part of the Framingham Heart Study. Quantile-specific heritabilities were calculated as: h2 =2βOP/(1+rspouse) and h2 ={(1+8rspouseβFS)0.5-1}/(2rspouse). RESULTS Heritability (h2 ± SE) of lipoprotein-associated phospholipase A2 (Lp-PLA2) mass concentrations increased from 0.11 ± 0.03 at the 10th percentile, 0.08 ± 0.03 at the 25th, 0.12 ± 0.03 at the 50th, 0.20 ± 0.04 at the 75th, and 0.26 ± 0.06 at the 90th percentile, or 0.0023 ± 0.0006 per each one-percent increase in the phenotype distribution (Plinear trend= 0.0004). Similarly, h2 increased 0.0029 ± 0.0011 (Plinear trend= 0.01) for sP-selectin, 0.0032 ± 0.0009 (Plinear trend= 0.0001) for soluble intercellular adhesion molecule 1 (sICAM-1), and 0.0026 ± 0.0006 for tumor necrosis factor receptor 2 (TNFR2) (Plinear trend= 5.0 × 10-6) per each one-percent increase in their distributions when estimated from βOP. Osteoprotegerin and soluble ST2 heritability also increased significantly with increasing percentiles of their distributions when estimated from βFS. Lp-PLA2 activity, CD40 ligand, TNFα, interleukin-18, and myeloperoxidase heritability showed no significant quantile-dependence. CONCLUSION The heritabilities of circulating Lp-PLA2-mass, sP-selectin, sICAM-1, TNFR2, osteoprotegerin and soluble ST2 concentrations are quantile-dependent, which may contribute to purported genetic modulations of: 1) sP-selectin's relationships to venous thrombosis, pulmonary hypertension, type 2 diabetes and atorvastatin treatment; 2) sICAM-I's relationships to brain abscess and atorvastatin treatment; and 3) Lp-PLA2's relationships to myocardial infarction and preeclampsia.
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Affiliation(s)
- Paul T Williams
- Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
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50
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Susai SR, Mongan D, Healy C, Cannon M, Nelson B, Markulev C, Schäfer MR, Berger M, Mossaheb N, Schlögelhofer M, Smesny S, Hickie IB, Berger GE, Chen EYH, de Haan L, Nieman DH, Nordentoft M, Riecher-Rössler A, Verma S, Thompson A, Yung AR, McGorry PD, Föcking M, Cotter D, Amminger GP. The association of plasma inflammatory markers with omega-3 fatty acids and their mediating role in psychotic symptoms and functioning: An analysis of the NEURAPRO clinical trial. Brain Behav Immun 2022; 99:147-156. [PMID: 34624483 DOI: 10.1016/j.bbi.2021.09.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 09/17/2021] [Accepted: 09/25/2021] [Indexed: 12/12/2022] Open
Abstract
There is increasing evidence that dysregulation of polyunsaturated fatty acids (FAs) mediated membrane function plays a role in the pathophysiology of schizophrenia. Even though preclinical findings have supported the anti-inflammatory properties of omega-3 FAs on brain health, their biological roles as anti-inflammatory agents and their therapeutic role on clinical symptoms of psychosis risk are not well understood. In the current study, we investigated the relationship of erythrocyte omega-3 FAs with plasma immune markers in a clinical high risk for psychosis (CHR) sample. In addition, a mediation analysis was performed to examine whether previously reported associations between omega-3 FAs and clinical outcomes were mediated via plasma immune markers. Clinical outcomes for CHR participants in the NEURAPRO clinical trial were measured using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Scale of Assessment of Negative Symptoms (SANS) and Social and Occupational Functioning Assessment Scale (SOFAS) scales. The erythrocyte omega-3 index [eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] and plasma concentrations of inflammatory markers were quantified at baseline (n = 268) and 6 month follow-up (n = 146) by gas chromatography and multiplex immunoassay, respectively. In linear regression models, the baseline plasma concentrations of Interleukin (IL)-15, Intercellular adhesion molecule (ICAM)-1 and Vascular cell adhesion molecule (VCAM)-1 were negatively associated with baseline omega-3 index. In addition, 6-month change in IL-12p40 and TNF-α showed a negative association with change in omega-3 index. In longitudinal analyses, the baseline and 6 month change in omega-3 index was negatively associated with VCAM-1 and TNF-α respectively at follow-up. Mediation analyses provided little evidence for mediating effects of plasma immune markers on the relationship between omega-3 FAs and clinical outcomes (psychotic symptoms and functioning) in CHR participants. Our results indicate a predominantly anti-inflammatory relationship of omega-3 FAs on plasma inflammatory status in CHR individuals, but this did not appear to convey clinical benefits at 6 month and 12 month follow-up. Both immune and non-immune biological effects of omega-3 FAs would be resourceful in understanding the clinical benefits of omega-3 FAs in CHR papulation.
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Affiliation(s)
- Subash Raj Susai
- Department of Psychiatry, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
| | - David Mongan
- Department of Psychiatry, RCSI University of Medicine and Health Sciences, Dublin, Ireland
| | - Colm Healy
- Department of Psychiatry, RCSI University of Medicine and Health Sciences, Dublin, Ireland
| | - Mary Cannon
- Department of Psychiatry, RCSI University of Medicine and Health Sciences, Dublin, Ireland
| | - Barnaby Nelson
- Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Orygen, 35 Poplar Rd, Parkville 3052, Australia
| | - Connie Markulev
- Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Orygen, 35 Poplar Rd, Parkville 3052, Australia
| | - Miriam R Schäfer
- Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Orygen, 35 Poplar Rd, Parkville 3052, Australia
| | - Maximus Berger
- Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Orygen, 35 Poplar Rd, Parkville 3052, Australia
| | - Nilufar Mossaheb
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Monika Schlögelhofer
- BioPsyC-Biopsychosocial Corporation - Non-Profit Association for Research Funding, Austria; Department of Child and Adolescent Psychiatry, Medical University Vienna, Austria
| | - Stefan Smesny
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
| | - Ian B Hickie
- Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Gregor E Berger
- Child and Adolescent Psychiatric Service of the Canton of Zurich, Zürich, Switzerland
| | - Eric Y H Chen
- Department of Psychiatry, University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Lieuwe de Haan
- Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands
| | - Dorien H Nieman
- Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands
| | - Merete Nordentoft
- Mental Health Center Copenhagen, Department of Clinical Medicine, Copenhagen University Hospital, Denmark
| | | | - Swapna Verma
- Institute of Mental Health, Singapore, Singapore
| | - Andrew Thompson
- Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Orygen, 35 Poplar Rd, Parkville 3052, Australia
| | - Alison Ruth Yung
- Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Orygen, 35 Poplar Rd, Parkville 3052, Australia; Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, Australia; School of Health Sciences, University of Manchester, UK
| | - Patrick D McGorry
- Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Orygen, 35 Poplar Rd, Parkville 3052, Australia
| | - Melanie Föcking
- Department of Psychiatry, RCSI University of Medicine and Health Sciences, Dublin, Ireland
| | - David Cotter
- Department of Psychiatry, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
| | - G Paul Amminger
- Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Orygen, 35 Poplar Rd, Parkville 3052, Australia; Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
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