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Yaslianifard S, Sameni F, Kazemi K, Atefpour Y, Hajikhani B, Baradaran Bagheri A, Yazdani S, Dadashi M. Beyond the gut: a comprehensive meta-analysis on Helicobacter pylori infection and cardiovascular complications. Ann Clin Microbiol Antimicrob 2025; 24:18. [PMID: 40102932 PMCID: PMC11916874 DOI: 10.1186/s12941-025-00788-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 03/03/2025] [Indexed: 03/20/2025] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is known to induce chronic inflammatory conditions, and interactions between the host immune system and pathogen have diverted attention toward investigating its correlation with extra-gastrointestinal disorders. OBJECTIVE The present study aimed to assess the rate of H. pylori infection in cardiovascular disease (CVD) through a systematic review and meta-analysis. METHODS We conducted a large-scale meta-analysis to determine the prevalence rates of H. pylori infection in vascular diseases. Articles from PubMed/Medline, Web of Science, and Embase databases published between 2000 and 2023 were included for analysis. We used multiple independent observers to extract data, calculated the pooled frequency of H. pylori in vascular diseases using a random effect model, and reported the results as a weighted average based on the study population. The main outcome measures were presented with 95% confidence intervals (CI). RESULTS In 87 included studies, the prevalence of H. pylori infection in vascular diseases was 56.7% worldwide. 14.25% of H. pylori isolates harbored the cagA gene. The predominant vascular complication was coronary artery disease (CAD) (31.07%), primarily documented in Europe. This meta-analysis revealed a declining emphasis on studying the association of H. pylori infection with vascular disease in recent times. CONCLUSION According to this meta-analysis, H. pylori infection has a high frequency in CVD and may increase the risk of vascular diseases. However, further research is required, particularly in nations with limited data.
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Affiliation(s)
- Somayeh Yaslianifard
- Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Fatemeh Sameni
- Department of Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran
- Molecular Microbiology Research Center, Faculty of Medicine, Shahed University, Tehran, Iran
| | - Kimia Kazemi
- Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Yousef Atefpour
- Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Bahareh Hajikhani
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Baradaran Bagheri
- Department of Neurosurgery, Shahid Madani Hospital, Alborz University of Medical Sciences, Karaj, Iran
| | - Shahrooz Yazdani
- Department of Cardiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
- Cardiovascular Research Center, Shahid Rajaei Hospital, Alborz University of Medical Sciences, Karaj, Iran.
| | - Masoud Dadashi
- Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.
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Saviano A, Morabito Loprete MR, Pignataro G, Piccioni A, Gasbarrini A, Franceschi F, Candelli M. Helicobacter pylori, Atherosclerosis, and Coronary Artery Disease: A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:346. [PMID: 40005462 PMCID: PMC11857399 DOI: 10.3390/medicina61020346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Revised: 02/11/2025] [Accepted: 02/14/2025] [Indexed: 02/27/2025]
Abstract
Coronary artery disease (CAD) is one of the leading causes of death worldwide, significantly contributing to mortality in both developed and developing nations. CAD arises from a combination of risk factors, including atherosclerosis, dyslipidemia, hypertension, diabetes, and smoking. In recent years, growing evidence has suggested a potential link between infectious agents and cardiovascular diseases. Among these, Helicobacter pylori (H. pylori) infection has been hypothesized for over a decade to play a role in the pathogenesis of CAD. This hypothesis is based on the bacterium's ability to trigger host inflammatory or autoimmune responses, potentially contributing to the progression of atherosclerotic plaques and coronary events. The association between H. pylori infection and CAD is of considerable interest as it opens new avenues for prevention and management strategies in cardiovascular health. Understanding this relationship could lead to innovative approaches to reducing the burden of CAD, particularly in populations with a high prevalence of H. pylori. In this review, we aim to provide a comprehensive overview of the most recent evidence on the involvement of H. pylori in the development and prognosis of CAD. By analyzing and synthesizing current findings, we seek to shed light on unresolved questions and clarify the ambiguous aspects of this potential connection. Our goal is to contribute to a deeper understanding of how H. pylori, may influence cardiovascular disease and to inspire further research in this critical area.
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Affiliation(s)
- Angela Saviano
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (A.S.); (M.R.M.L.); (G.P.); (A.P.); (F.F.)
| | - Maria Rita Morabito Loprete
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (A.S.); (M.R.M.L.); (G.P.); (A.P.); (F.F.)
| | - Giulia Pignataro
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (A.S.); (M.R.M.L.); (G.P.); (A.P.); (F.F.)
| | - Andrea Piccioni
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (A.S.); (M.R.M.L.); (G.P.); (A.P.); (F.F.)
| | - Antonio Gasbarrini
- Medical and Surgical Science Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy;
| | - Francesco Franceschi
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (A.S.); (M.R.M.L.); (G.P.); (A.P.); (F.F.)
| | - Marcello Candelli
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (A.S.); (M.R.M.L.); (G.P.); (A.P.); (F.F.)
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Chui ESH, Chan AKY, Ng ACK, Teh MYM, Ho HC, Chan YC. Mechanism and clinical implication of gut dysbiosis in degenerative abdominal aortic aneurysm: A systematic review. Asian J Surg 2024; 47:5088-5095. [PMID: 38772822 DOI: 10.1016/j.asjsur.2024.05.058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 04/27/2024] [Accepted: 05/10/2024] [Indexed: 05/23/2024] Open
Abstract
The gut microbiome is the entirety of microorganisms and their genomes residing in the gut, characterised by diversity, stability, and resilience. Disrupted gut microbiome has been implicated in multiple disease entities. The aim of this paper is to summarise the rapidly evolving contemporary evidence of gut dysbiosis on the development and progression of abdominal aortic aneurysm (AAA), discuss possible mechanisms, and explore potential microbiota-targeted interventions and prognostic markers for AAA. A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, using PubMed, ScienceDirect, Web of Science, Ovid, Embase. Search terms of "microbiome" OR "dysbiosis" OR "microorganism"; AND "aneurysm" OR "dilatation" OR "aorta" were used. Study endpoints included effects of microbiota on AAA formation, effects of specific type of bacteria and its metabolite on AAA formation, and pre- or post-treatment by novel small-molecules/inhibitors. From May to August 2023, a total of twelve animal studies and eight human studies were included. Akkermansia muciniphila, Lactobacillus acidophilus and species from the Bacteroidetes phylum were associated with lower AAA incidence in both animal and human studies, while Proteobacteria phylum, Campylobacter, Fusobacterium and Faecalibacterium prausnitzii were found to be in abundance in the AAA group and were associated with larger aneurysms. The diversity of gut microbiota was inversely correlated with AAA diameter. Three important mechanisms were identified: including trimethylamine N-oxide pathway, butyric acid pathway, and aberrant tryptophan metabolism. With our expanding knowledge of the downstream pathogenic mechanisms of gut dysbiosis, novel therapeutics such as short-chain fatty acids and spermidine, as well as prognostic biomarkers such as TMAO have yielded promising preclinical results. In conclusion, there is strong evidence corroborating the role of gut dysbiosis in the pathogenesis of AAA, wherein its therapeutic and prognostic potential deserves further exploration.
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Affiliation(s)
- Ernest S H Chui
- Division of Vascular & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre, South Wing, 14th Floor K Block, Queen Mary Hospital, Hong Kong Special Administrative Region
| | - Aidan K Y Chan
- Division of Vascular & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre, South Wing, 14th Floor K Block, Queen Mary Hospital, Hong Kong Special Administrative Region
| | - Anson C K Ng
- Division of Vascular & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre, South Wing, 14th Floor K Block, Queen Mary Hospital, Hong Kong Special Administrative Region
| | - Margaret Y M Teh
- Division of Vascular & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre, South Wing, 14th Floor K Block, Queen Mary Hospital, Hong Kong Special Administrative Region
| | - Haris C Ho
- Division of Vascular & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre, South Wing, 14th Floor K Block, Queen Mary Hospital, Hong Kong Special Administrative Region
| | - Yiu Che Chan
- Division of Vascular & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre, South Wing, 14th Floor K Block, Queen Mary Hospital, Hong Kong Special Administrative Region.
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Davis TME, Bruce DG, Schimke K, Chubb SAP, Davis WA. The inter-relationship between Helicobacter pylori infection, dementia and mortality in type 2 diabetes: The Fremantle Diabetes Study Phase I. J Diabetes Complications 2024; 38:108854. [PMID: 39244938 DOI: 10.1016/j.jdiacomp.2024.108854] [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: 04/18/2024] [Revised: 08/24/2024] [Accepted: 09/04/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND Given sparse relevant data, the aim of this study was to determine whether Helicobacter pylori infection, including cytotoxin-associated gene-A (CagA) producing strains, is associated with dementia in type 2 diabetes (T2DM). METHODS Longitudinal data from 1115 participants in the community-based Fremantle Diabetes Study Phase I (mean age 64.0 years, 48.0 % males; 38.0 % H. pylori seronegative, 24.3 % H. pylori seropositive/CagA seronegative, and 37.7 % H. pylori/CagA seropositive at baseline) were analyzed. RESULTS During up to 19 years of follow-up, 50.3 % and 83.5 % of participants without and with incident dementia, respectively, died. In Cox proportional hazards models, H. pylori/CagA seropositivity (hazard ratio (95 % CI) 1.68 (1.15, 2.46), P = 0.008), but not H. pylori seropositivity/CagA seronegativity (P = 0.541) was an independent predictor of incident dementia, but neither H. pylori seropositivity/CagA seronegativity nor H. pylori/CagA seropositivity were significant predictors in competing risks models (P ≥ 0.280). CONCLUSIONS Although CagA seropositivity in T2DM may have a contributory etiologic role in the risk of dementia, this may be through its association with reduced cardiovascular/all-cause mortality.
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Affiliation(s)
- Timothy M E Davis
- University of Western Australia, Medical School, Fremantle Hospital, PO Box 480, Fremantle, Western Australia 6959, Australia; Department of Endocrinology and Diabetes, Fiona Stanley and Fremantle Hospitals Group, 11 Robin Warren Drive, Murdoch, Western Australia 6150, Australia.
| | - David G Bruce
- University of Western Australia, Medical School, Fremantle Hospital, PO Box 480, Fremantle, Western Australia 6959, Australia
| | - Katrin Schimke
- University of Western Australia, Medical School, Fremantle Hospital, PO Box 480, Fremantle, Western Australia 6959, Australia; Center Practice, Neumarkt 1, St Leonhardstrasse 35, 9000 St Gallen, Switzerland
| | - S A Paul Chubb
- University of Western Australia, Medical School, Fremantle Hospital, PO Box 480, Fremantle, Western Australia 6959, Australia
| | - Wendy A Davis
- University of Western Australia, Medical School, Fremantle Hospital, PO Box 480, Fremantle, Western Australia 6959, Australia
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Fang Y, Fan C, Li Y, Xie H. The influence of Helicobacter pylori infection on acute coronary syndrome and lipid metabolism in the Chinese ethnicity. Front Cell Infect Microbiol 2024; 14:1437425. [PMID: 39290976 PMCID: PMC11405380 DOI: 10.3389/fcimb.2024.1437425] [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: 05/27/2024] [Accepted: 08/16/2024] [Indexed: 09/19/2024] Open
Abstract
Background Acute coronary syndrome (ACS) patients frequently present a relatively high prevalence of Helicobacter pylori (H. pylori) infection. H. pylori was previously hypothesized to induce ACS through the regulation of lipid levels. However, the risk of H. pylori-induced ACS varies significantly among different ethnic groups, and the associations between H. pylori and lipid parameters remain unclear. This study aimed to systematically assess the risk of ACS in Chinese populations with H. pylori infection while also evaluating the effects of H. pylori on lipid parameters. Materials and methods A hospital-based case-control study involving 280 participants was conducted. Immunoblotting was used for the detection and genotyping of H. pylori. The associations between H. pylori and ACS, as well as lipid parameters, were analyzed via the chi-square test and a multiple logistic regression model. Results H. pylori infection significantly increased the risk of ACS among all participants (adjusted odds ratio (OR) = 4.04, 95% confidence interval (CI): 1.76-9.25, P < 0.05), with no associations with virulence factors (cytotoxin-associated gene A (CagA) or vacuole toxin geneA (VacA)). Subgroup analysis revealed a significant increase in the risk of ACS among the elderly population aged 56-64 years with H. pylori infection. Additionally, a substantial association was observed between H. pylori and acute myocardial infarction (AMI). No significant differences were found in lipid parameters, including low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and the LDL/HDL ratio, between individuals positive and negative for H. pylori infection. Similar results were observed between the ACS group and the control group. Conclusions Our study has demonstrated for the first time that H. pylori does not significantly impact lipid metabolism but increases the risk of ACS fourfold in the Chinese population (OR = 4.04, 95% CI: 1.76-9.25). Furthermore, the virulence factors of H. pylori (CagA and VacA) may not be involved in the mechanisms by which they promote the development of ACS. This finding provides additional evidence for the association between H. pylori and ACS among different ethnic groups and refutes the biological mechanism by which H. pylori affects ACS through lipid metabolism regulation. Regular screening for H. pylori and eradication treatment in elderly individuals and those at high risk for ACS may be effective measures for reducing the incidence of ACS. Future research should include multicenter randomized controlled trials and explore host genetics and the effects of H. pylori on the gut microbiota as potential biological pathways linking H. pylori and ACS.
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Affiliation(s)
- Yizhen Fang
- Department of Clinical Laboratory, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Department of Clinical Laboratory, Xiamen Key Laboratory of Precision Medicine for Cardiovascular Disease, Xiamen, China
| | - Chunming Fan
- Department of Clinical Laboratory, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Department of Clinical Laboratory, Xiamen Key Laboratory of Precision Medicine for Cardiovascular Disease, Xiamen, China
| | - Yun Li
- Blood Transfusion Department, Affiliated Fuzhou First Hospital of Fujian Medical University, Fuzhou, China
| | - Huabin Xie
- Department of Clinical Laboratory, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Department of Clinical Laboratory, Xiamen Key Laboratory of Precision Medicine for Cardiovascular Disease, Xiamen, China
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Jeon EB, Kim N, Kim BJ, Hwang IC, Kim SB, Kim JH, Choi Y, Jun YK, Yoon H, Shin CM, Park YS, Lee DH, Ahn S. Risk of Ischemic Stroke in Relation to Helicobacter pylori Infection and Eradication Status: A Large-Scale Prospective Observational Cohort Study. Gut Liver 2024; 18:642-653. [PMID: 38712396 PMCID: PMC11249949 DOI: 10.5009/gnl230458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 02/26/2024] [Accepted: 03/14/2024] [Indexed: 05/08/2024] Open
Abstract
Background/Aims : A few studies have suggested the association between Helicobacter pylori (HP) infection and ischemic stroke. However, the impact of HP eradication on stroke risk has not been well evaluated. This study aimed to assess the influence of HP eradication on the incidence of ischemic stroke, considering the potential effect of sex. Methods : This prospective observational cohort study was conducted at Seoul National University Bundang Hospital, from May 2003 to February 2023, and involved gastroscopy-based HP testing. Propensity score (PS) matching was employed to ensure balanced groups by matching patients in the HP eradicated group (n=2,803) in a 3:1 ratio with patients in the HP non-eradicated group (n=960). Cox proportional hazard regression analysis was used to evaluate the risk of ischemic stroke. Results : Among 6,664 patients, multivariate analysis after PS matching indicated that HP eradication did not significantly alter the risk of ischemic stroke (hazard ratio, 0.531; 95% confidence interval, 0.221 to 1.270; p=0.157). Sex-specific subgroup analyses, both univariate and multivariate, did not yield statistically significant differences. However, Kaplan-Meier analysis revealed a potential trend: the females in the HP eradicated group exhibited a lower incidence of ischemic stroke than those in the HP non-eradicated group, although this did not reach statistical significance (p=0.057). Conclusions : This finding suggests that HP eradication might not impact the risk of ischemic stroke. However, there was a trend showing that females potentially had a lower risk of ischemic stroke following HP eradication, though further investigation is required to establish definitive evidence.
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Affiliation(s)
- Eun-Bi Jeon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea
| | - Beom Joon Kim
- Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - In-Chang Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sang Bin Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Ji-Hyun Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yonghoon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yu Kyung Jun
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea
| | - Soyeon Ahn
- Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea
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Ozturk S, Dursun MA, Yildirim T, Sargin F, Sargin ZG, Ozan ZT. Traditional and nontraditional lipid parameters in Helicobacter pylori infection. Biomark Med 2024; 18:291-300. [PMID: 38530363 PMCID: PMC11218799 DOI: 10.2217/bmm-2023-0453] [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: 08/01/2023] [Accepted: 01/25/2024] [Indexed: 03/27/2024] Open
Abstract
Aims: This study sought to evaluate the relationship between Helicobacter pylori infection and traditional and nontraditional lipid parameters, including atherogenic index of plasma, cardiogenic risk ratio, atherogenic coefficient and remnant cholesterol. Methods: After the application of exclusion criteria, 309 patients were allocated according to the absence (n = 52) or presence (n = 257) of H. pylori infection. Results: Total cholesterol, low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were nonsignificantly higher, and HDL-C levels were nonsignificantly lower, in the H. pylori-infected patient group. Triglyceride-to-HDL-C ratio, LDL-C-to-HDL-C ratio, atherogenic index of plasma, cardiogenic risk ratio, atherogenic coefficient and remnant cholesterol were comparable among groups. Conclusion: There was no significant association between H. pylori infection and traditional and nontraditional novel lipid parameters and indices.
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Affiliation(s)
- Selcuk Ozturk
- Kırıkkale Yuksek Ihtisas Hospital, Department of Cardiology, Kırıkkale, Turkey
| | - Muhammed A Dursun
- Kestel State Hospital, Department of Internal Medicine, Bursa, Turkey
| | - Tekin Yildirim
- Yozgat Bozok University Faculty of Medicine, Department of Internal Medicine, Yozgat, Turkey
| | - Fatih Sargin
- Kırıkkale Yuksek Ihtisas Hospital, Department of Anesthesiology, Kırıkkale, Turkey
| | - Zeynep G Sargin
- Kırıkkale University Faculty of Medicine, Department of Gastroenterology, Kırıkkale, Turkey
| | - Zeynep T Ozan
- Yozgat Bozok University Faculty of Medicine, Department of Internal Medicine, Yozgat, Turkey
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Sun M, Chen H, Dong S, Zhang G, Zhou X, Cheng H. Alteration of gut microbiota in post-stroke depression patients with Helicobacter pylori infection. Neurobiol Dis 2024; 193:106458. [PMID: 38423194 DOI: 10.1016/j.nbd.2024.106458] [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: 09/19/2023] [Revised: 02/26/2024] [Accepted: 02/26/2024] [Indexed: 03/02/2024] Open
Abstract
BACKGROUND Several studies have identified an association between the gut microbiome and post-stroke depression(PSD), and Helicobacter pylori(H. pylori) infection cause significant alterations in the composition of the gastrointestinal microbiome. However, evidence regarding the role of the H. pylori infection in promoting PSD is still lacking. Here, we conducted a retrospective study to explore risk factors associated with PSD. METHODS Patients with cerebral infarction were consecutively enrolled from December 2021 to October 2022. The diagnosis of PSD is based on the DSM-V criteria, and the Hamilton Depression Rating Scale(HAMD) was used to identify patients with PSD. White matter lesions were evaluated using magnetic resonance imaging(MRI) and H. pylori infection was detected by 13C-urea breath test. Further, 16S rRNA gene sequencing was used to evaluate the changes in gut microbiota composition of fecal samples from PSD patients. The concentration of short-chain fatty acids(SCFAs) was determined by gas chromatography-mass spectrometry(GC-MS). RESULTS Multivariate regression analysis showed that deep white matter lesions(DWMLs) [odds ratio(OR) 3.382, 95% confidence interval(CI) 1.756-6.512; P = 0.001] and H. pylori infection(OR 2.186, 95% CI 1.149-4.159; P = 0.017) were the independent risk factors for PSD. Patients with H. pylori infection had more severe depressive symptoms than patients without infection. Intestinal microbiota was significantly different between H. pylori-positive PSD[H. pylori(+)] patients and H. pylori-negative PSD[H. pylori (-)] patients. Fecal SCFAs concentrations were significantly reduced in the H. pylori(+) group compared to the negative ones. CONCLUSION DWMLs and H. pylori infection may play important roles in the development of PSD. H. pylori infection is likely to be involved in the pathogenesis of PSD by altering the intestinal flora.
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Affiliation(s)
- Mei Sun
- Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Han Chen
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
| | - Siyu Dong
- Department of Neurology, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, China.
| | - Guoxin Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
| | - Xiaoying Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
| | - Hong Cheng
- Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
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Jung JM, Gruber A, Heseltine P, Rajamani K, Ameriso SF, Fisher MJ. New Directions in Infection-Associated Ischemic Stroke. J Clin Neurol 2024; 20:140-152. [PMID: 38330416 PMCID: PMC10921058 DOI: 10.3988/jcn.2023.0056] [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: 02/07/2023] [Revised: 09/06/2023] [Accepted: 11/12/2023] [Indexed: 02/10/2024] Open
Abstract
The relationship between infections and stroke has not been fully characterized, probably delaying the development of specific treatments. This narrative review addresses mechanisms of stroke linked to infections, including hypercoagulability, endothelial dysfunction, vasculitis, and impaired thrombolysis. SARS-CoV-2, the virus that causes COVID-19, may promote the development of stroke, which may represent its most severe neurological complication. The development of specific therapies for infection-associated stroke remains a profound challenge. Perhaps the most important remaining issue is the distinction between infections that trigger a stroke versus infections that are truly incidental. This distinction likely requires the establishment of appropriate biomarkers, candidates of which are elevated levels of fibrin D-dimer and anticardiolipin/antiphospholipid antibodies. These candidate biomarkers might have potential use in identifying pathogenic infections preceding stroke, which is a precursor to establishing specific therapies for this syndrome.
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Affiliation(s)
- Jin-Man Jung
- Department of Neurology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea; Korea University Zebrafish, Translational Medical Research Center, Ansan, Korea
| | | | - Peter Heseltine
- Division of Infectious Diseases, Department of Medicine, University of California, Irvine, Irvine, CA, USA
| | - Kumar Rajamani
- Department of Neurology, Wayne State University-Detroit Medical Center, Detroit, MI, USA
| | - Sebastián F Ameriso
- Division of Vascular Neurology, Department of Neurology, Fleni, Autonomous City of Buenos Aires, Argentina
| | - Mark J Fisher
- Department of Neurology, University of California Irvine Medical Center, Orange, CA, USA.
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Ciarambino T, Crispino P, Minervini G, Giordano M. Role of Helicobacter pylori Infection in Pathogenesis, Evolution, and Complication of Atherosclerotic Plaque. Biomedicines 2024; 12:400. [PMID: 38398002 PMCID: PMC10886498 DOI: 10.3390/biomedicines12020400] [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: 08/08/2023] [Revised: 09/11/2023] [Accepted: 02/07/2024] [Indexed: 02/25/2024] Open
Abstract
The therapeutic management of atherosclerosis focuses almost exclusively on the reduction of plasma cholesterol levels. An important role in the genesis and evolution of atherosclerosis is played by chronic inflammation in promoting thrombosis phenomena after atheroma rupture. This review aims to take stock of the knowledge so far accumulated on the role of endemic HP infection in atherosclerosis. The studies produced so far have demonstrated a causal relationship between Helicobacter pylori (HP) and CVD. In a previous study, we demonstrated in HP-positive patients that thrombin and plasma fragment 1 + 2 production was proportionally related to tumor necrosis factor-alpha levels and that eradication of the infection resulted in a reduction of inflammation. At the end of our review, we can state that HP slightly affects the risk of CVD, particularly if the infection is associated with cytotoxic damage, and HP screening could have a clinically significant role in patients with a high risk of CVD. Considering the high prevalence of HP infection, an infection screening could be of great clinical utility in patients at high risk of CVD.
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Affiliation(s)
- Tiziana Ciarambino
- Internal Medicine Department, Hospital of Marcianise, ASL Caserta, 81037 Caserta, Italy
| | - Pietro Crispino
- Internal Medicine Department, Hospital of Latina, ASL Latina, 04100 Latina, Italy;
| | - Giovanni Minervini
- Internal Medicine Department, Hospital of Lagonegro, AOR San Carlo, 85042 Lagonegro, Italy;
| | - Mauro Giordano
- Department of Advanced Medical and Surgical Sciences, University of Campania “L. Vanvitelli”, 81100 Naples, Italy;
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Wärme J, Sundqvist MO, Hjort M, Agewall S, Collste O, Ekenbäck C, Frick M, Henareh L, Hofman-Bang C, Spaak J, Sörensson P, Y-Hassan S, Svensson P, Lindahl B, Hofmann R, Tornvall P. Helicobacter pylori and Pro-Inflammatory Protein Biomarkers in Myocardial Infarction with and without Obstructive Coronary Artery Disease. Int J Mol Sci 2023; 24:14143. [PMID: 37762446 PMCID: PMC10531769 DOI: 10.3390/ijms241814143] [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: 08/10/2023] [Revised: 09/05/2023] [Accepted: 09/14/2023] [Indexed: 09/29/2023] Open
Abstract
Myocardial infarction (MI) with obstructive coronary artery disease (MI-CAD) and MI in the absence of obstructive coronary artery disease (MINOCA) affect different populations and may have separate pathophysiological mechanisms, with greater inflammatory activity in MINOCA compared to MI-CAD. Helicobacter pylori (Hp) can cause systemic inflammation and has been associated with cardiovascular disease (CVD). We aimed to investigate whether Hp infection is associated with concentrations of protein biomarkers of inflammation and CVD. In a case-control study, patients with MINOCA (n = 99) in Sweden were included, complemented by matched subjects with MI-CAD (n = 99) and controls (n = 100). Protein biomarkers were measured with a proximity extension assay in plasma samples collected 3 months after MI. The seroprevalence of Hp and cytotoxin-associated gene A (CagA) was determined using ELISA. The associations between protein levels and Hp status were studied with linear regression. The prevalence of Hp was 20.2%, 19.2%, and 16.0% for MINOCA, MI-CAD, and controls, respectively (p = 0.73). Seven proteins were associated with Hp in an adjusted model: tissue plasminogen activator (tPA), interleukin-6 (IL-6), myeloperoxidase (MPO), TNF-related activation-induced cytokine (TRANCE), pappalysin-1 (PAPPA), soluble urokinase plasminogen activator receptor (suPAR), and P-selectin glycoprotein ligand 1 (PSGL-1). Hp infection was present in one in five patients with MI, irrespective of the presence of obstructive CAD. Inflammatory proteins were elevated in Hp-positive subjects, thus not ruling out that Hp may promote an inflammatory response and potentially contribute to the development of CVD.
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Affiliation(s)
- Jonatan Wärme
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden
- Department of Cardiology, Södersjukhuset, SE-118 83 Stockholm, Sweden
| | - Martin O. Sundqvist
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden
- Department of Cardiology, Södersjukhuset, SE-118 83 Stockholm, Sweden
| | - Marcus Hjort
- Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden
- Uppsala Clinical Research Center, Uppsala University, SE-751 85 Uppsala, Sweden
| | - Stefan Agewall
- Division of Medicine, Institute of Clinical Medicine, University of Oslo, NO-0318 Oslo, Norway
- Department of Cardiology, Oslo University Hospital, NO-0450 Oslo, Norway
| | - Olov Collste
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden
- Department of Cardiology, Södersjukhuset, SE-118 83 Stockholm, Sweden
| | - Christina Ekenbäck
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, SE-182 88 Stockholm, Sweden
| | - Mats Frick
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden
- Department of Cardiology, Södersjukhuset, SE-118 83 Stockholm, Sweden
| | - Loghman Henareh
- Department of Medicine Huddinge, Karolinska Institute, SE-141 86 Huddinge, Sweden
- Coronary Artery Disease Area, Heart and Vascular Theme, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
| | - Claes Hofman-Bang
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, SE-182 88 Stockholm, Sweden
| | - Jonas Spaak
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, SE-182 88 Stockholm, Sweden
| | - Peder Sörensson
- Coronary Artery Disease Area, Heart and Vascular Theme, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
- Department of Medicine Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden
| | - Shams Y-Hassan
- Department of Medicine Huddinge, Karolinska Institute, SE-141 86 Huddinge, Sweden
- Coronary Artery Disease Area, Heart and Vascular Theme, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
| | - Per Svensson
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden
- Department of Cardiology, Södersjukhuset, SE-118 83 Stockholm, Sweden
| | - Bertil Lindahl
- Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden
- Uppsala Clinical Research Center, Uppsala University, SE-751 85 Uppsala, Sweden
| | - Robin Hofmann
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden
- Department of Cardiology, Södersjukhuset, SE-118 83 Stockholm, Sweden
| | - Per Tornvall
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden
- Department of Cardiology, Södersjukhuset, SE-118 83 Stockholm, Sweden
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12
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Bacterial Infections and Atherosclerosis – A Mini Review. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2022. [DOI: 10.22207/jpam.16.3.08] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Atherosclerosis is the most challenging subsets of coronary artery disease in humans, in which risk factors emerge from childhood, and its prevalence increases with age. Experimental research demonstrates that infections due to bacteria stimulate atherogenic events. Atherosclerosis has complex pathophysiology that is linked with several bacterial infections by damaging the inner arterial wall and heart muscles directly and indirectly by provoking a systemic pro-inflammation and acute-phase protein. Repeated bacterial infections trigger an inflammatory cascade that triggers immunological responses that negatively impact cardiovascular biomarkers includes triglycerides, high-density lipoprotein, C-reactive protein, heat shock proteins, cytokines, fibrinogen, and leukocyte count. Herein, we intended to share the role of bacterial infection in atherosclerosis and evaluate existing evidence of animal and human trials on the association between bacterial infections and atherosclerosis on update.
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Antibodies towards TVLLPVIFF Amino Acid Sequence of TNF Receptor Induced by Helicobacter pylori in Patients with Coronary Heart Disease. J Clin Med 2022; 11:jcm11092545. [PMID: 35566671 PMCID: PMC9103578 DOI: 10.3390/jcm11092545] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 04/14/2022] [Accepted: 04/29/2022] [Indexed: 02/07/2023] Open
Abstract
Background: Molecular mimicry between Helicobacter pylori (Hp) and the host components resulting in induction of cross-reacting antibodies has been suggested as accessory mechanism in the development of coronary heart disease (CHD). A potential target for antibodies induced during Hp infection by the components of these bacteria might be amino acid sequence TVLLPVIFF (P1) of tumor necrosis factor receptor (TNFR), which is exposed on vascular endothelium and immunocompetent cells, driving inflammation. Aim: To examine whether anti-P1 IgG are induced during Hp infection in CHD patients. Methods: Sera from CHD patients infected with Hp (54) vs. sera of uninfected healthy donors (22) were tested by the ELISA for anti-H. pylori antibodies, anti-P1 IgG, and for antibodies towards control sequence IAKEGFEKIS (P2). Sera of Caviae porcellus infected experimentally with Hp (30) or uninfected (10) were included into this study. The same serum samples, which were positive for anti-P1 IgG, were adsorbed with Hp and then subjected to the ELISA. The biological activity of anti-P1 IgG was assessed in complement (C1q) binding assay. Results: Sera of 43 CHD patients seropositive for anti-Hp IgG contained anti-P1 IgG binding C1q. Additionally, 10 serum samples of animals seropositive for anti-Hp IgG contained anti-P1 IgG. Anti-P1 IgG in tested sera were neutralized by their adsorption with Hp. Conclusion: In CHD patients infected with Hp, antibodies cross-reacting with TNFR common sequence are produced. Further studies are necessary to define immunogenic Hp determinants and to confirm possible cellular effects of cross-reacting antibodies.
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Zhang P, He Q, Song D, Wang Y, Liu X, Ding G, Xing W. Association of Helicobacter pylori Infection With Carotid Atherosclerosis in a Northern Chinese Population: A Cross-Sectional Study. Front Cardiovasc Med 2022; 8:795795. [PMID: 35174222 PMCID: PMC8841728 DOI: 10.3389/fcvm.2021.795795] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 12/30/2021] [Indexed: 11/13/2022] Open
Abstract
Numerous studies have shown that Helicobacter pylori (HP) infection may be involved in the development of carotid atherosclerosis (CAS), but this conclusion is still controversial. The aim of this study was to explore whether there is a positive association between HP infection and CAS occurrence. We collected data on demographic characteristics, lifestyle, and disease history of the participants by questionnaire. We obtained clinical anthropometric data and blood samples of the participants from clinical examinations and laboratory work. The 13C urea breath test (13C-UBT) was performed to assess the HP infection status, and carotid ultrasonography was used to diagnose the CAS and plaque types. Univariate analysis and multivariate logistic regression were used to identify the relationship between HP infection and CAS. A total of 1,424 participants were recruited for this study. A total of 740 HP-positive individuals and 684 HP-negative individuals were identified, and 345 participants were diagnosed with CAS. The prevalence of CAS was higher in the HP-positive group (26.4%) than in the HP-negative group (21.7%) (P < 0.05). A significantly higher prevalence of carotid intima-media thickening, carotid plaque, and carotid stenosis was identified in the HP-positive group than in the HP-negative group (P < 0.05). There was no significant difference in the detection rate of unstable plaques between the HP-positive and HP-negative groups (P > 0.05). In multivariate models adjusted for covariates, HP infection showed a positive association with CAS, independent of other risk factors (ORs range: 1.283–1.333, P < 0.05). HP infection independently accounted for approximately 5% of the CAS risk in the absence of other cardiovascular risk factors. A positive association between HP infection and CAS was demonstrated in this study. HP infection might be an independent risk factor for CAS. Although the effect of HP infection on CAS observed in our study was less than that of traditional risk factors, we believe that this is an indispensable advance in the etiological study of CAS. These results imply that the microbial population might play an essential role in CAS, which provides a new perspective for the primary prevention of CAS.
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15
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Elhadidy AA, Basiouny MA. Evaluation of Helicobacter pylori infection as a potential risk factor of acute ischemic cerebrovascular stroke. ALEXANDRIA JOURNAL OF MEDICINE 2021. [DOI: 10.1080/20905068.2021.1990550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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Abstract
Abstract
Helicobacter cinaedi (H. cinaedi) is a Gram-negative curved motile rod that causes bloodstream or enteric infections. It was suggested that H. cinaedi was involved in the progression of atherosclerosis. We aimed to investigate the presence of H. cinaedi DNA using a nested-polymerase chain reaction (PCR) in atheroma plaques from patients with atherosclerosis-induced vascular diseases. A total of 129 patients diagnosed with valvular heart disease due to atherosclerosis and 146 patients with non-atherosclerotic post-stenotic dilatation were included as the patient and the control groups, respectively. The ATCC BA847 H. cinaedi strain was used as the positive control for the nested-PCR method. We investigated H. cinaedi DNA in our study groups using the nested-PCR method and detected only six H. cinaedi DNA (4.65%) in the 129 atherosclerotic patient group. We detected significant difference between patient and control groups with respect to the presence of H. cinaedi on the basis of Fischer’s exact test (p = 0.010) by univariate analysis. Age (OR: 1.042, p = 0.016), total cholesterol (≥200 mg/dL) (OR: 1.849, p = 0.0001), and high-density lipoprotein (≥50 mg/dL) (OR: 0.745, p = 0.039) levels were detected as independent variables for the risk of atherosclerosis development in the patient group. The presence of H. cinaedi was not detected as an independent variable in a multivariate analysis. Previous studies suggested that H. cinaedi-induced oral infections might translocate to vascular tissue and induce chronic inflammation in the aorta, which subsequently may lead to atherosclerotic plaque formation. In conclusion, we could not suggest that there is a causal relationship between H. cinaedi and the development of atherosclerosis. However, age (OR: 1.042), total cholesterol (≥200 mg/dL, OR: 1.849), and high-density lipoprotein (≥50 mg/dL, OR: 0.745, as protective) levels have a significant role in the pathogenesis of atherosclerosis development. We also suggest that the presence of H. cinaedi may contribute to the risk of atherosclerosis development due to the univariate comparison result.
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17
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Talari HR, Moniri R, Mollaghanbari M, Haddad Kashani H, Jalalian MN. Evaluating the relationship between Helicobacter pylori infection and carotid intima-media thickness a cross sectional study. Ann Med Surg (Lond) 2021; 69:102659. [PMID: 34471528 PMCID: PMC8387901 DOI: 10.1016/j.amsu.2021.102659] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 08/03/2021] [Accepted: 08/03/2021] [Indexed: 12/11/2022] Open
Abstract
Introduction Helicobacter pylori is a gram-negative spiral bacterium that is frequently found in the human stomach. Significant association has been reported between Cytotoxin associated gene A (CagA)- positive Helicobacter pylori strains and coronary heart disease. The aim of the present study is to investigate the carotid intima-media thickness as an indicator of atherosclerosis in people with Helicobacter pylori infection. Methods This study was done on patients who underwent upper GI endoscopy and biopsy, and after obtaining conscious consent underwent ultrasound of the right and left carotid arteries for measuring carotid intima-media thickness (CIMT) and blood tests. Results In this study, 90 patients who underwent upper GI endoscopy were examined in three groups: negative H. pylori negative, positive cagA and negative cagA. The right, left and average of CIMT in cagA-positive group were significantly higher than the other two groups (p < 0.05). Howerver, the average of CIMT was not significantly different between men and women. Also, the hsCRP average level in positive cagA group was significantly higher than other groups (p < 0.05). Conclusion Our findings suggest that there is an increase in CIMT values in patients with H. pylori infection, especially in cases of positive cagA. The positive cagA group showed significantly higher levels of hs-CRP, as a marker of elevated inflammatory response. Therefore, H. pylori infection, especially cagA-positive strains and its associated systemic inflammatory response can be considered as a contributing factor in atherosclerosis and cardiovascular disease.
H.pylori infection especially in case of positive CagA+ caused the right/left CIMT increase. Higher levels of inflammation in H.pylori, CagA patients and atherosclerosis risk factors couldn’t cause the significant difference. H.pylori infection with positive CagA and its inflammation is an important factor in atherosclerosis and cardiovascular diseases.
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Affiliation(s)
- Hamid Reza Talari
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.,Department of Radiology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Rezvan Moniri
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammadreza Mollaghanbari
- Department of Internal Medicine, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Haddad Kashani
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Naser Jalalian
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.,Department of Radiology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
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18
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Doheim MF, Altaweel AA, Elgendy MG, Elshanbary AA, Dibas M, Ali AAHA, Dahy TM, Sharaf AK, Hassan AE. Association between Helicobacter Pylori infection and stroke: a meta-analysis of 273,135 patients. J Neurol 2021; 268:3238-3248. [PMID: 32447554 DOI: 10.1007/s00415-020-09933-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 05/16/2020] [Accepted: 05/19/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Stroke stands among the most leading causes of mortality worldwide. Although modifiable risk factors for stroke have been identified, current risk factors do not sufficiently explain the risk in young patients. Previous studies have postulated an association between infection by Helicobacter pylori (HP) and stroke. OBJECTIVE To investigate the association between HP infection and stroke by using a systematic review and meta-analysis approach. METHODS Four electronic search engines/libraries were systematically searched for relevant observational studies. Studies were screened for eligibility and data were extracted. The odds ratio (OR) and 95% confidence interval (95% CI) were combined under the random-effect model. The protocol was registered in PROSPERO (CRD42019123689). RESULTS Among the included studies, 25 studies were analyzed for anti-HP IgG, 9 studies were for anti-Cag A, and 6 studies were for the C-urea breath test. The results showed that positive anti-HP IgG was significantly associated with an increased risk of stroke [OR (95% CI) = 1.43 (1.25-1.46)]. Similarly, both antiCag A and C-urea breath test were significantly associated with an increased risk of stroke with [OR (95% CI) = 1.77 (1.25-2.49)], and [OR (95% CI) = 2.21 (1.33-3.66)], respectively. Furthermore, our results indicated that positive anti-HP IgG was associated with stroke caused by atherothrombosis and small artery disease. CONCLUSIONS This study suggests that HP infection is significantly associated with increased risk of stroke. However, more well-designed studies are required to investigate if early HP eradication might decrease the incidence of stroke.
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Affiliation(s)
| | | | | | | | - Mahmoud Dibas
- College of Medicine, Sulaiman Al Rajhi University, Qassim, Saudi Arabia
| | | | | | | | - Ameer E Hassan
- Department of Neurology, University of Texas Rio Grande Valley, Valley Baptist Medical Center, Harlingen, TX, USA.
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Ninomiya R, Kubo S, Baba T, Kajiwara T, Tokunaga A, Nabeka H, Doihara T, Shimokawa T, Matsuda S, Murakami K, Aigaki T, Yamaoka Y, Hamada F. Inhibition of low-density lipoprotein uptake by Helicobacter pylori virulence factor CagA. Biochem Biophys Res Commun 2021; 556:192-198. [PMID: 33845309 DOI: 10.1016/j.bbrc.2021.03.170] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 03/30/2021] [Indexed: 01/01/2023]
Abstract
Helicobacter pylori (H. pylori) infection mainly causes gastroduodenal diseases, including chronic gastritis, peptic ulcer disease and gastric cancer. In recent years, several studies have demonstrated that infection with H. pylori, especially strains harboring the virulence factor CagA (cytotoxin-associated gene A), contribute to the development of non-gastric systemic diseases, including hypercholesterolemia and atherosclerotic cardiovascular diseases. However, mechanisms underlying this association has not been defined. In this study, we carried out a large-scale genetic screen using Drosophila and identified a novel CagA target low-density lipoprotein receptor (LDLR), which aids in the clearance of circulating LDL. We showed that CagA physically interacted with LDLR via its carboxy-terminal region and inhibited LDLR-mediated LDL uptake into cells. Since deficiency of LDLR-mediated LDL uptake has been known to increase plasma LDL and accelerate atherosclerosis, our findings may provide a novel mechanism for the association between infection with CagA-positive H. pylori and hypercholesterolemia leading to atherosclerotic cardiovascular diseases.
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Affiliation(s)
- Ryo Ninomiya
- Department of Anatomy, Faculty of Medicine, Oita University, Yufu, Oita, 879-5593, Japan
| | - Shuichi Kubo
- Department of Anatomy, Faculty of Medicine, Oita University, Yufu, Oita, 879-5593, Japan
| | - Takehiro Baba
- Department of Anatomy, Faculty of Medicine, Oita University, Yufu, Oita, 879-5593, Japan
| | - Tooru Kajiwara
- Department of Anatomy, Faculty of Medicine, Oita University, Yufu, Oita, 879-5593, Japan
| | - Akinori Tokunaga
- Division of Laboratory Animal Resources, Life Science Research Laboratory, University of Fukui, Eiheiji, Fukui, 910-1193, Japan
| | - Hiroaki Nabeka
- Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan
| | - Takuya Doihara
- Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan
| | - Tetsuya Shimokawa
- Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan
| | - Seiji Matsuda
- Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, 879-5593, Japan
| | - Toshiro Aigaki
- Department of Biological Sciences, Tokyo Metropolitan University, Hachioji, Tokyo, 192-0397, Japan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Oita, 879-5593, Japan; Department of Gastroenterology and Hepatology, Baylor College of Medicine and Michael DeBakey Veterans Affairs Medical Center, Houston, TX, 77030-4211, USA
| | - Fumihiko Hamada
- Department of Anatomy, Faculty of Medicine, Oita University, Yufu, Oita, 879-5593, Japan.
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Kalani M, Hodjati H, Ghoddusi Johari H, Doroudchi M. Memory T cells of patients with abdominal aortic aneurysm differentially expressed micro RNAs 21, 92a, 146a, 155, 326 and 663 in response to Helicobacter pylori and Lactobacillus acidophilus. Mol Immunol 2020; 130:77-84. [PMID: 33246580 DOI: 10.1016/j.molimm.2020.11.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 10/21/2020] [Accepted: 11/09/2020] [Indexed: 12/21/2022]
Abstract
Regarding the role of micro RNAs (miRNA) in the proliferation and differentiation of T cells as well as the controversy around the role of bacteria in the pathogenesis of abdominal aortic aneurysm (AAA), the effects of Helicobacter pylori (Hp) and Lactobacillus acidophilus (La) were investigated in the induction of miRNAs and apoptosis in CD4+ memory T (Tem) cells of AAA patients and controls. Signature atherosclerosis miRNAs 21, 92a, 146a, 155, 326 and 663 were measured in the sera and tissues of AAA patients and control. PBMCs separately and in co-culture with HUVEC were treated with Hp-water-extract (HpWE) and La-conditioned-medium (LaCM). Apoptosis and miRNA levels were assessed in the isolated Tem by flowcytometry and real-time-PCR. In single-culture, HpWE increased apoptosis and miR-155 and LaCM decreased apoptosis and increased miR-21. In co-culture, apoptosis decreased in both groups in response to CagA+HpWE. Also, all miRNAs increased in patients Tem but in controls, only miR- 146a and 21 showed changes. Although, apoptosis was similar in Tem of patients and controls, the effects of Hp and La were different on the induction of apoptosis and miRNAs and also these bacteria showed different impacts in single and co-culture conditions. Beyond the direct effects of these bacteria on the pathogenesis of diseases, their effects on miRNAs expression may shed light on their roles in the development and the prevention of AAA.
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Affiliation(s)
- Mehdi Kalani
- Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Immunology, Professor Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Hodjati
- Department of Vascular Surgery, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamed Ghoddusi Johari
- Department of Vascular Surgery, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehrnoosh Doroudchi
- Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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Association between Helicobacter pylori Infection and Colorectal Adenomatous Polyps. Gastroenterol Res Pract 2019; 2019:7480620. [PMID: 31929786 PMCID: PMC6935790 DOI: 10.1155/2019/7480620] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Accepted: 11/27/2019] [Indexed: 02/07/2023] Open
Abstract
Background Helicobacter pylori infection is a common chronic infection worldwide. At the same time, the incidence of colorectal adenomatous polyps is also at high levels. In order to assess the relationship between Helicobacter pylori infection and the occurrence of colorectal adenomatous polyps, we observed 166 patients who had undergone an electronic colonoscopy and 13C urea breath test in the outpatient clinic. Method A total of 166 (87 males and 79 females, aged 53.85 ± 9.18 years) patients who had colonoscopy examination and 13C urea breath test were divided into a Helicobacter pylori-positive group (n = 68) and Helicobacter pylori-negative group (n = 98) by the 13C urea breath test. At the same time, total cholesterol, triglycerides, and fasting blood sugar were measured and the occurrence of hypertension was counted. Results Patients with Helicobacter pylori infection had higher incidence of colorectal adenomatous polyps and multiple colorectal adenomatous polyps, higher levels of total cholesterol and fasting glucose, and more males (P < 0.05, P < 0.01). It was found that Helicobacter pylori infection (P < 0.05, OR 2.383) was significantly associated with the risk of colorectal adenomatous polyps by binary logistic regression analysis. Conclusions Patients with Helicobacter pylori infection had higher incidence of colorectal adenomatous polyps.
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Testerman TL, Semino-Mora C, Cann JA, Qiang B, Peña EA, Liu H, Olsen CH, Chen H, Appt SE, Kaplan JR, Register TC, Merrell DS, Dubois A. Both diet and Helicobacter pylori infection contribute to atherosclerosis in pre- and postmenopausal cynomolgus monkeys. PLoS One 2019; 14:e0222001. [PMID: 31490998 PMCID: PMC6730863 DOI: 10.1371/journal.pone.0222001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 08/20/2019] [Indexed: 02/07/2023] Open
Abstract
A number of viruses and bacterial species have been implicated as contributors to atherosclerosis, potentially providing novel pathways for prevention. Epidemiological studies examining the association between Helicobacter pylori and cardiovascular disease have yielded variable results and no studies have been conducted in nonhuman primates. In this investigation, we examined the relationship between H. pylori infection and atherosclerosis development in socially housed, pre- and postmenopausal cynomolgus macaques consuming human-like diets. Ninety-four premenopausal cynomolgus monkeys (Macaca fascicularis) were fed for 36 months an atherogenic diet deriving its protein from either casein lactalbumin(CL) or high isoflavone soy (SOY). Animals were then ovariectomized and fed either the same or the alternate diet for an additional 36 months. Iliac artery biopsies were obtained at the time of ovariectomy and iliac and coronary artery sections were examined at the end of the study. Evidence of H. pylori infection was found in 64% of the monkeys and 46% of animals had live H. pylori within coronary atheromas as determined by mRNA-specific in situ hybridization. There was a significant linear relationship between the densities of gastric and atheroma organisms. Helicobactor pylori infection correlated with increased intimal plaque area and thickness at both the premenopausal and postmenopausal time points and regardless of diet (p< 0.01), although animals consuming the SOY diet throughout had the least amount of atherosclerosis. Additionally, plasma lipid profiles, intimal collagen accumulation, ICAM-1, and plaque macrophage densities were adversely affected by H. pylori infection among animals consuming the CL diet, while the SOY diet had the opposite effect. Plaque measurements were more highly associated with the densities of cagA-positive H. pylori within coronary atheromas than with the densities of gastric organisms, whereas plasma lipid changes were associated with H. pylori infection, but not cagA status. This study provides strong evidence that live H. pylori infects atheromas, exacerbates atherosclerotic plaque development, and alters plasma lipid profiles independently of diet or hormonal status. Finally, socially subordinate animals relative to their dominant counterparts had a greater prevalence of H. pylori, suggesting a stress effect. The results indicate that early H. pylori eradication could prevent or delay development of cardiovascular disease.
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Affiliation(s)
- Traci L. Testerman
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, United States of America
| | - Cristina Semino-Mora
- Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America
| | | | - Beidi Qiang
- Department of Mathematics and Statistics, Southern Illinois University at Edwardsville, Edwardsville, IL, United States of America
| | - Edsel A. Peña
- Department of Statistics, University of South Carolina, Columbia, SC, United States of America
| | - Hui Liu
- Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America
| | - Cara H. Olsen
- Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America
| | - Haiying Chen
- Wake Forest University Primate Center, Wake Forest University School of Medicine, Winston-Salem, NC, United States of America
| | - Susan E. Appt
- Wake Forest University Primate Center, Wake Forest University School of Medicine, Winston-Salem, NC, United States of America
| | - Jay R. Kaplan
- Wake Forest University Primate Center, Wake Forest University School of Medicine, Winston-Salem, NC, United States of America
| | - Thomas C. Register
- Wake Forest University Primate Center, Wake Forest University School of Medicine, Winston-Salem, NC, United States of America
| | - D. Scott Merrell
- Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America
| | - Andre Dubois
- Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America
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The Impacts of Peptic Ulcer on Functional Outcomes of Ischemic Stroke. J Stroke Cerebrovasc Dis 2018; 28:311-316. [PMID: 30391329 DOI: 10.1016/j.jstrokecerebrovasdis.2018.09.056] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 09/19/2018] [Accepted: 09/30/2018] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND AND PURPOSE Studies have shown that peptic ulcer increased the risk of ischemic stroke and stroke recurrence. This study aimed to evaluate the impacts of peptic ulcer on functional outcomes of ischemic stroke. METHODS Patients with first-ever ischemic stroke were grouped as with and without history of peptic ulcer. Functional outcomes were evaluated with modified Rankin scale at 90 days after the index stroke. Favorable functional outcomes were defined as with a modified Rankin scale score of 0-2. Logistic regression was used to identify predictors for favorable functional outcomes at 90 days. RESULTS Among the 2577 enrolled patients with ischemic stroke, 129 (5.0%) had a history of peptic ulcer. The proportion of favorable outcome was higher in patients without peptic ulcer than those with (59.3% versus 42.6%, P < .001). Multivariate logistic analysis detected that history of peptic ulcer (odds ratio [OR] = 2.89, 95% confidence interval [CI], 1.03-8.10, P = .043), National Institute of Health Stroke Scale score (OR = 2.11, 95% CI, 1.79-2.48, P < .001), and large-artery atherosclerosis stroke subtype (OR = 4.08, 95% CI, 1.11-15.03, P = .035) decreased the likelihood of favorable outcomes. CONCLUSIONS Ischemic stroke patients with peptic ulcer may have an increased risk of less favorable neurological outcome at 90 days after the index stroke.
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Tikhomirova TS, Galzitskaya OV. Functionally Significant Amino Acid Motifs of Heat Shock Proteins: Structural and Bioinformatics Analyses of Hsp60/Hsp10 in Five Classes of Chordata. Mol Biol 2018. [DOI: 10.1134/s0026893318050138] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
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Abstract
Helicobacter pylori infection is the principal cause of peptic ulcer disease, gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue lymphoma. Recent studies have shown that it may interfere with many biological processes and determine or influence the occurrence of many diseases outside the stomach. Currently, the role of H. pylori in idiopathic thrombocytopenic purpura and iron deficiency anemia is well documented. Emerging evidence suggests that it may also contribute to vitamin B12 deficiency, insulin resistance, metabolic syndrome, diabetes mellitus and non-alcoholic liver disease. Additionally, it may increase the risk of acute coronary syndrome, cerebrovascular disease, neurodegenerative disease and other miscellaneous disorders. Different pathogenic mechanisms have been hypothesized, including the occurrence of molecular mimicry and the induction of a low-grade inflammation. This review summarizes the results of the most relevant studies on the extra-gastroduodenal manifestations of H. pylori infection.
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Affiliation(s)
- Feng-Woei Tsay
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, 386 Ta Chung 1st Road, Kaohsiung, 813 Taiwan, Republic of China
- Cheng Shiu University, Kaohsiung, Taiwan, Republic of China
| | - Ping-I Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, 386 Ta Chung 1st Road, Kaohsiung, 813 Taiwan, Republic of China
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Maev IV, Bakulin IG, Kurilovich SA, Bakulina NV, Andreev NG, Golubev NN. Helicobacter pylori and extragastroduodenal diseases: the proven facts and assumptions. DOKAZATEL'NAYA GASTROENTEROLOGIYA 2018; 7:45. [DOI: 10.17116/dokgastro2018703145] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Helicobacter pylori infection and atherosclerosis: is there a causal relationship? Eur J Clin Microbiol Infect Dis 2017; 36:2293-2301. [DOI: 10.1007/s10096-017-3054-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 06/20/2017] [Indexed: 12/14/2022]
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Kyaw T, Peter K, Li Y, Tipping P, Toh BH, Bobik A. Cytotoxic lymphocytes and atherosclerosis: significance, mechanisms and therapeutic challenges. Br J Pharmacol 2017; 174:3956-3972. [PMID: 28471481 DOI: 10.1111/bph.13845] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Revised: 04/02/2017] [Accepted: 04/24/2017] [Indexed: 02/06/2023] Open
Abstract
Cytotoxic lymphocytes encompass natural killer lymphocytes (cells) and cytotoxic T cells that include CD8+ T cells, natural killer (NK) T cells, γ, δ (γδ)-T cells and human CD4 + CD28- T cells. These cells play critical roles in inflammatory diseases and in controlling cancers and infections. Cytotoxic lymphocytes can be activated via a number of mechanisms that may involve dendritic cells, macrophages, cytokines or surface proteins on stressed cells. Upon activation, they secrete pro-inflammatory cytokines as well as anti-inflammatory cytokines, chemokines and cytotoxins to promote inflammation and the development of atherosclerotic lesions including vulnerable lesions, which are strongly implicated in myocardial infarctions and strokes. Here, we review the mechanisms that activate and regulate cytotoxic lymphocyte activity, including activating and inhibitory receptors, cytokines, chemokine receptors-chemokine systems utilized to home to inflamed lesions and cytotoxins and cytokines through which they affect other cells within lesions. We also examine their roles in human and mouse models of atherosclerosis and the mechanisms by which they exert their pathogenic effects. Finally, we discuss strategies for therapeutically targeting these cells to prevent the development of atherosclerotic lesions and vulnerable plaques and the challenge of developing highly targeted therapies that only minimally affect the body's immune system, avoiding the complications, such as increased susceptibility to infections, which are currently associated with many immunotherapies for autoimmune diseases. LINKED ARTICLES This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc.
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Affiliation(s)
- Tin Kyaw
- Baker Heart and Diabetes Institute, Melbourne, Vic, Australia.,Department of Medicine, Monash University, Melbourne, Vic, Australia
| | - Karlheinz Peter
- Baker Heart and Diabetes Institute, Melbourne, Vic, Australia.,Department of Immunology, Monash University, Melbourne, Vic, Australia
| | - Yi Li
- Baker Heart and Diabetes Institute, Melbourne, Vic, Australia.,Department of Medicine, Monash University, Melbourne, Vic, Australia
| | - Peter Tipping
- Department of Medicine, Monash University, Melbourne, Vic, Australia
| | - Ban-Hock Toh
- Baker Heart and Diabetes Institute, Melbourne, Vic, Australia.,Department of Medicine, Monash University, Melbourne, Vic, Australia
| | - Alex Bobik
- Baker Heart and Diabetes Institute, Melbourne, Vic, Australia.,Department of Immunology, Monash University, Melbourne, Vic, Australia.,Department of Medicine, Monash University, Melbourne, Vic, Australia
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Review. The Link between Periodontal Disease, Inflammation and Atherosclerosis — an Interdisciplinary Approach. JOURNAL OF INTERDISCIPLINARY MEDICINE 2017. [DOI: 10.1515/jim-2017-0016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Abstract
Periodontal disease is a chronic inflammatory disease that results from the activity of altered oral microbiome, leading to altered immune reaction, destruction of tissues supporting the teeth, and oral bone loss. This disease is particularly associated with an expressed systemic inflammation, being considered nowadays an inflammatory disorder. At the same time, inflammation has been recognized to play a major role in the development of atherosclerotic lesions. Atheromatous plaque formation is triggered by alterations in the structure of the endothelium, which lead to the expression of adhesion molecules and recruitment of immune cells such as macrophages, in the arterial wall. While the association between periodontal disease, inflammation and cardiovascular diseases has been well established, the causality relation between these three entities has not been demonstrated so far. This review presents the most common advances in understanding the complex link between periodontal disease, inflammation and atherosclerosis, as a common pathway leading to increased cardiovascular risk.
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Kramer CD, Genco CA. Microbiota, Immune Subversion, and Chronic Inflammation. Front Immunol 2017; 8:255. [PMID: 28348558 PMCID: PMC5346547 DOI: 10.3389/fimmu.2017.00255] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 02/21/2017] [Indexed: 12/12/2022] Open
Abstract
Several host-adapted pathogens and commensals have evolved mechanisms to evade the host innate immune system inducing a state of low-grade inflammation. Epidemiological studies have also documented the association of a subset of these microorganisms with chronic inflammatory disorders. In this review, we summarize recent studies demonstrating the role of the microbiota in chronic inflammatory diseases and discuss how specific microorganisms subvert or inhibit protective signaling normally induced by toll-like receptors (TLRs). We highlight our work on the oral pathogen Porphyromonas gingivalis and discuss the role of microbial modulation of lipid A structures in evasion of TLR4 signaling and resulting systemic immunopathology associated with atherosclerosis. P. gingivalis intrinsically expresses underacylated lipid A moieties and can modify the phosphorylation of lipid A, leading to altered TLR4 signaling. Using P. gingivalis mutant strains expressing distinct lipid A moieties, we demonstrated that expression of antagonist lipid A was associated with P. gingivalis-mediated systemic inflammation and immunopathology, whereas strains expressing agonist lipid A exhibited modest systemic inflammation. Likewise, mice deficient in TLR4 were more susceptible to vascular inflammation after oral infection with P. gingivalis wild-type strain compared to mice possessing functional TLR4. Collectively, our studies support a role for P. gingivalis-mediated dysregulation of innate and adaptive responses resulting in immunopathology and systemic inflammation. We propose that anti-TLR4 interventions must be designed with caution, given the balance between the protective and destructive roles of TLR signaling in response to microbiota and associated immunopathologies.
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Affiliation(s)
- Carolyn D Kramer
- Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine , Boston, MA , USA
| | - Caroline Attardo Genco
- Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine , Boston, MA , USA
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Chhibber-Goel J, Singhal V, Bhowmik D, Vivek R, Parakh N, Bhargava B, Sharma A. Linkages between oral commensal bacteria and atherosclerotic plaques in coronary artery disease patients. NPJ Biofilms Microbiomes 2016. [PMID: 28649401 PMCID: PMC5460270 DOI: 10.1038/s41522-016-0009-7] [Citation(s) in RCA: 106] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Coronary artery disease is an inflammatory disorder characterized by narrowing of coronary arteries due to atherosclerotic plaque formation. To date, the accumulated epidemiological evidence supports an association between oral bacterial diseases and coronary artery disease, but has failed to prove a causal link between the two. Due to the recent surge in microbial identification and analyses techniques, a number of bacteria have been independently found in atherosclerotic plaque samples from coronary artery disease patients. In this study, we present meta-analysis from published studies that have independently investigated the presence of bacteria within atherosclerotic plaque samples in coronary artery disease patients. Data were collated from 63 studies covering 1791 patients spread over a decade. Our analysis confirms the presence of 23 oral commensal bacteria, either individually or in co-existence, within atherosclerotic plaques in patients undergoing carotid endarterectomy, catheter-based atherectomy, or similar procedures. Of these 23 bacteria, 5 (Campylobacter rectus, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Prevotella nigrescens) are unique to coronary plaques, while the other 18 are additionally present in non-cardiac organs, and associate with over 30 non-cardiac disorders. We have cataloged the wide spectrum of proteins secreted by above atherosclerotic plaque-associated bacteria, and discuss their possible roles during microbial migration via the bloodstream. We also highlight the prevalence of specific poly-microbial communities within atherosclerotic plaques. This work provides a resource whose immediate implication is the necessity to systematically catalog landscapes of atherosclerotic plaque-associated oral commensal bacteria in human patient populations. A review of bacterial populations in the mouth and in diseased arteries will help research into the role of bacteria in heart disease. Amit Sharma and colleagues at the International Centre for Genetic Engineering and Biotechnology, with co-workers at the All India Institute of Medical Sciences, both in New Delhi, India, analyzed 63 studies covering 1791 patients spread over a decade. They summarize evidence of 23 types of oral bacteria that are also found in atherosclerotic plaques in artery walls. The review also cataloged the proteins secreted by the bacteria and discussed possible involvement of these proteins in the migration of bacteria through the bloodstream. Full genetic details are available for 19 of the 23 bacterial species, which should greatly assist further investigations into the significance of bacteria in the onset of heart disease.
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Affiliation(s)
- Jyoti Chhibber-Goel
- Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
| | - Varsha Singhal
- Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
| | - Debaleena Bhowmik
- Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
| | - Rahul Vivek
- Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
| | - Neeraj Parakh
- Cardiothoracic Sciences Centre, All India Institute of Medical Sciences, New Delhi, India
| | - Balram Bhargava
- Cardiothoracic Sciences Centre, All India Institute of Medical Sciences, New Delhi, India
| | - Amit Sharma
- Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
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Badran HM, Mahfouz ME. Cytotoxin-associated gene-A bearing strains of Helicobacter pylori and atrial fibrillation due to ischemic origin: is there a link? ACTA ACUST UNITED AC 2016; 14:518-20. [PMID: 17667641 DOI: 10.1097/hjr.0b013e328011a2a0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Background Helicobacter pylori CagA strains could increase the risk for atrial fibrillation in patients with coronary artery disease Methods Serological status for H. pylori CagA using enzyme-linked immunosorbent assay, C-reactive protein, total leucocytic count and atrial size were determined in 185 coronary artery disease patients (with and without atrial fibrillation) and 80 healthy subjects (control). Results CagA strain showed a higher prevalence in the atrial fibrillation group. Atrial dimension and C-reactive protein (independent predictors of atrial fibrillation) were significantly increased in the CagA seropositive subgroup Conclus ons There is a strong liaison between H. pylori CagA infection and atrial fibrillation in coronary artery disease. Increased C reactive protein and atrial size in atrial fibrillation patients may reflect atrial inflammatory remodeling.
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Affiliation(s)
- Hala Mahfouz Badran
- Cardiology Department, Faculty of Medicine, Menoufiya University, Shebin El-Koom, Egypt.
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Slocum C, Kramer C, Genco CA. Immune dysregulation mediated by the oral microbiome: potential link to chronic inflammation and atherosclerosis. J Intern Med 2016; 280:114-28. [PMID: 26791914 DOI: 10.1111/joim.12476] [Citation(s) in RCA: 90] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Cardiovascular disease is an inflammatory disorder characterized by the progressive formation of plaque in coronary arteries, termed atherosclerosis. It is a multifactorial disease that is one of the leading causes of death worldwide. Although a number of risk factors have been associated with disease progression, the underlying inflammatory mechanisms contributing to atherosclerosis remain to be fully delineated. Within the last decade, the potential role for infection in inflammatory plaque progression has received considerable interest. Microbial pathogens associated with periodontal disease have been of particular interest due to the high levels of bacteremia that are observed after routine dental procedures and every day oral activities, such as tooth brushing. Here, we explore the potential mechanisms that may explain how periodontal pathogens either directly or indirectly elicit immune dysregulation and consequently progressive inflammation manifested as atherosclerosis. Periodontal pathogens have been shown to contribute directly to atherosclerosis by disrupting endothelial cell function, one of the earliest indicators of cardiovascular disease. Oral infection is thought to indirectly induce elevated production of inflammatory mediators in the systemic circulation. Recently, a number of studies have been conducted focusing on how disruption of the gut microbiome influences the systemic production of proinflammatory cytokines and consequently exacerbation of inflammatory diseases such as atherosclerosis. It is clear that the immune mechanisms leading to atherosclerotic plaque progression, by oral infection, are complex. Understanding the immune pathways leading to disease progression is essential for the future development of anti-inflammatory therapies for this chronic disease.
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Affiliation(s)
| | - C Kramer
- Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA
| | - C A Genco
- Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA
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Yang W, Xuan C. Influence of Helicobacter pylori Infection on Metabolic Syndrome in Old Chinese People. Gastroenterol Res Pract 2016; 2016:6951264. [PMID: 27429613 PMCID: PMC4939336 DOI: 10.1155/2016/6951264] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2016] [Revised: 05/03/2016] [Accepted: 06/05/2016] [Indexed: 12/12/2022] Open
Abstract
Background. H. pylori infection is one of the most common chronic infectious inflammatory diseases worldwide and is also a risk factor for atherosclerosis. Patients with metabolic syndrome are known to be at increased risk for atherosclerosis. The aim of our study was to assess the effects of H. pylori infection on serum lipids, body mass index (BMI), and metabolic syndrome in old Chinese people. Material and Method. A total of 191 (133 males and 58 females, aged 73.19 ± 11.03 years) people who had gastroscopy examination in our hospital were divided into H. pylori-positive group (n = 80) and H. pylori-negative group (n = 111). H. pylori infection was diagnosed by rapid urease test. Results. Patients with H. pylori infection had higher BMI and fasting glucose levels and incidence of metabolic syndrome (p < 0.01). It was found that BMI (p < 0.01, OR 74.469), H. pylori infection (p < 0.01, OR 5.427), total cholesterol (p < 0.01, OR 15.544), and diabetes mellitus (p < 0.01, OR 23.957) were significantly associated with the risk of metabolic syndrome by binary logistic regression analysis. Conclusions. Patients with H. pylori infection had higher BMI and fasting glucose levels and had incidence of metabolic syndrome.
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Affiliation(s)
- Wen Yang
- Geriatric Digestive System Department, Navy General Hospital, No. 6 Fuchenglu Road, Beijing 100048, China
| | - Cunfu Xuan
- Department of Cardiology, Shuozhou People's Hospital, No. 263 ShanYang Street, Shuocheng District, Shuozhou, Shanxi 036002, China
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Kim J, Seo M, Kim SK, Bae YS. Flagellin-induced NADPH oxidase 4 activation is involved in atherosclerosis. Sci Rep 2016; 6:25437. [PMID: 27146088 PMCID: PMC4857127 DOI: 10.1038/srep25437] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Accepted: 04/18/2016] [Indexed: 02/06/2023] Open
Abstract
It is widely accepted that bacterial infection-mediated inflammation facilitates development of atherosclerosis by activating toll-like receptor (TLR) signaling system. We reasoned that NADPH oxidases (Nox), required for TLR-mediated inflammatory response, are involved in atherogenesis. Here, we show that the activation of Nox4 through TLR5 regulates the inflammation of the endothelium and in atherogenesis. Flagellin-induced interaction between the COOH region of Nox4 and the TIR domain of TLR5 led to H2O2 generation, which in turn promoted the secretion of pro-inflammatory cytokines including IL-8, as well as the expression of ICAM-1 in human aortic endothelial cells (HAECs). Knockdown of the Nox4 in HAECs resulted in attenuated expressions of IL-8 and ICAM-1 leading to a reduction in the adhesion and trans-endothelial migration of monocytes. Challenge of recombinant FliC (rFliC) to the ApoE KO mice with high-fat diet (HFD) resulted in significantly increased atherosclerotic plaque sizes compared to the saline-injected mice. However, an injection of rFliC into the Nox4ApoE DKO mice with HFDs failed to generate atherosclerotic plaque, suggesting that Nox4 deficiency resulted in significant protections against rFliC-mediated atherogenesis. We conclude that TLR5-dependent Nox4 activation and subsequent H2O2 generation play critical roles for the development of atherosclerosis.
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Affiliation(s)
- Jinoh Kim
- Department of Life Science, Ewha Womans University, Seoul, Korea
| | - Misun Seo
- Department of Life Science, Ewha Womans University, Seoul, Korea
| | - Su Kyung Kim
- Department of Life Science, Ewha Womans University, Seoul, Korea
| | - Yun Soo Bae
- Department of Life Science, Ewha Womans University, Seoul, Korea
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ANDREOLLA HF, BONA LRD, SANDER GB, MAZZOLENI LE, TAVARES RG, PROLLA JC. LACK OF ASSOCIATION BETWEEN HELICOBACTER PYLORI'S VIRULENCE AND INCREASED SERUM C-REACTIVE PROTEIN LEVELS IN FUNCTIONAL DYSPEPTIC PATIENTS. ARQUIVOS DE GASTROENTEROLOGIA 2016; 53:49-54. [PMID: 27281505 DOI: 10.1590/s0004-28032016000100010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Accepted: 09/12/2015] [Indexed: 01/15/2023]
Abstract
ABSTRACT Background Recently, a great variety of studies aimed to investigate and even suggestHelicobacter pylori as an important key factor in gastrointestinal and non-gastrointestinal events development. The well-established relationship between bacterial virulence and increased risk for peptic ulcer or gastric carcinoma is not so clear when comparing inflammation markers alterations, such C-reactive protein, with the pathogen. Objective The objective of this study was to evaluate the presence of H. pylori, bacterial virulence and C-reactive protein serum levels in individuals diagnosed with functional dyspepsia. Methods Were prospectively included in this study 489 dyspeptic individuals. They fulfill Rome III clinical criteria for the diagnosis of functional dyspepsia with no organic disease at endoscopy. The bacterial infection was established by histology and urease rapid test. The levels of serum C-reactive protein were obtained by immunonefelometry and CagA status ofH. pylori positive individuals was determined through an imunoenzimatic assay. Results Prevalence rate of H. pylori was 66.3% and virulence factor CagA was detected in nearly 43% of positive samples. In addition, it has been noticed an association between Ilex paraguariensis(yerba maté) consumption and pathogen's prevalence. An important effect of bacterial infection on inflammation was only observed in gastric epithelium. Conclusion No systemic response to the pathogen, measured through C-reactive protein levels, was observed, regardless of CagA status. Otherwise, the intake of yerba maté should be considered as a cultural factor possibly related toH. pylori's transmission.
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Affiliation(s)
| | | | | | - Luiz Edmundo MAZZOLENI
- Universidade Federal do Rio Grande do Sul, Brazil; Hospital de Clínicas de Porto Alegre, Brasil
| | | | - João Carlos PROLLA
- Universidade Federal do Rio Grande do Sul, Brazil; Hospital de Clínicas de Porto Alegre, Brasil
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Abstract
PURPOSE OF REVIEW We have summarized available evidence for and against the presence of a vascular microbiome. Studies that have attempted to detect bacteria and viruses in blood vessels in both health and disease are critiqued in an attempt to explain contrary results that may be due to variations in methodology. RECENT FINDINGS Many studies have demonstrated the presence of both bacteria and viruses within diseased blood vessels. Evidence is most compelling in atherosclerosis; however, recent reports have raised questions about the potential role of microbes in nonatherosclerotic aortic aneurysms and vasculitis. Preliminary evidence also suggests that apparently normal vessels may harbor microbes. With the exception of certain viral infections (e.g. hepatitis C virus, HIV, Epstein-Barr virus, and cytomegalovirus) and infectious endocarditis, systemic vasculitides have not been convincingly associated with infectious agents. However, emerging data suggest that different communities of microbes may be present in noninflammatory and inflammatory large-vessel diseases. Whether variations in vascular microbial communities are the cause or a secondary result (epiphenomena) of vessel injury remains to be determined. SUMMARY Blood vessels may not be sterile. Future studies of microbes in vessel health and disease may provide important insights into disease pathogenesis and suggest new therapies for diseases now considered to be idiopathic and refractory.
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Shimoda A, Ueda K, Nishiumi S, Murata-Kamiya N, Mukai SA, Sawada SI, Azuma T, Hatakeyama M, Akiyoshi K. Exosomes as nanocarriers for systemic delivery of the Helicobacter pylori virulence factor CagA. Sci Rep 2016. [PMID: 26739388 DOI: 10.10.38/srep18346] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
CagA, encoded by cytotoxin-associated gene A (cagA), is a major virulence factor of Helicobacter pylori, a gastric pathogen involved in the development of upper gastrointestinal diseases. Infection with cagA-positive H. pylori may also be associated with diseases outside the stomach, although the mechanisms through which H. pylori infection promotes extragastric diseases remain unknown. Here, we report that CagA is present in serum-derived extracellular vesicles, known as exosomes, in patients infected with cagA-positive H. pylori (n = 4). We also found that gastric epithelial cells inducibly expressing CagA secrete exosomes containing CagA. Addition of purified CagA-containing exosomes to gastric epithelial cells induced an elongated cell shape, indicating that the exosomes deliver functional CagA into cells. These findings indicated that exosomes secreted from CagA-expressing gastric epithelial cells may enter into circulation, delivering CagA to distant organs and tissues. Thus, CagA-containing exosomes may be involved in the development of extragastric disorders associated with cagA-positive H. pylori infection.
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Affiliation(s)
- Asako Shimoda
- Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
- Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int'tech Center, Katsura, Nishikyo-ku, Kyoto 615-8530, Japan
| | - Koji Ueda
- Division of Biosciences, Functional Proteomics Center, Graduate School of Frontier Sciences, the University of Tokyo, CREST hall 1F, Institute of Medical Science, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
| | - Shin Nishiumi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan
| | - Naoko Murata-Kamiya
- Department of Microbiology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan
| | - Sada-Atsu Mukai
- Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
- Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int'tech Center, Katsura, Nishikyo-ku, Kyoto 615-8530, Japan
| | - Shin-ichi Sawada
- Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
- Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int'tech Center, Katsura, Nishikyo-ku, Kyoto 615-8530, Japan
| | - Takeshi Azuma
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan
| | - Masanori Hatakeyama
- Department of Microbiology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan
| | - Kazunari Akiyoshi
- Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
- Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int'tech Center, Katsura, Nishikyo-ku, Kyoto 615-8530, Japan
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Shimoda A, Ueda K, Nishiumi S, Murata-Kamiya N, Mukai SA, Sawada SI, Azuma T, Hatakeyama M, Akiyoshi K. Exosomes as nanocarriers for systemic delivery of the Helicobacter pylori virulence factor CagA. Sci Rep 2016; 6:18346. [PMID: 26739388 PMCID: PMC4703974 DOI: 10.1038/srep18346] [Citation(s) in RCA: 92] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 11/16/2015] [Indexed: 02/08/2023] Open
Abstract
CagA, encoded by cytotoxin-associated gene A (cagA), is a major virulence factor of Helicobacter pylori, a gastric pathogen involved in the development of upper gastrointestinal diseases. Infection with cagA-positive H. pylori may also be associated with diseases outside the stomach, although the mechanisms through which H. pylori infection promotes extragastric diseases remain unknown. Here, we report that CagA is present in serum-derived extracellular vesicles, known as exosomes, in patients infected with cagA-positive H. pylori (n = 4). We also found that gastric epithelial cells inducibly expressing CagA secrete exosomes containing CagA. Addition of purified CagA-containing exosomes to gastric epithelial cells induced an elongated cell shape, indicating that the exosomes deliver functional CagA into cells. These findings indicated that exosomes secreted from CagA-expressing gastric epithelial cells may enter into circulation, delivering CagA to distant organs and tissues. Thus, CagA-containing exosomes may be involved in the development of extragastric disorders associated with cagA-positive H. pylori infection.
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Affiliation(s)
- Asako Shimoda
- Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.,Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int'tech Center, Katsura, Nishikyo-ku, Kyoto 615-8530, Japan
| | - Koji Ueda
- Division of Biosciences, Functional Proteomics Center, Graduate School of Frontier Sciences, the University of Tokyo, CREST hall 1F, Institute of Medical Science, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
| | - Shin Nishiumi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan
| | - Naoko Murata-Kamiya
- Department of Microbiology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan
| | - Sada-Atsu Mukai
- Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.,Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int'tech Center, Katsura, Nishikyo-ku, Kyoto 615-8530, Japan
| | - Shin-ichi Sawada
- Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.,Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int'tech Center, Katsura, Nishikyo-ku, Kyoto 615-8530, Japan
| | - Takeshi Azuma
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan
| | - Masanori Hatakeyama
- Department of Microbiology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan
| | - Kazunari Akiyoshi
- Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.,Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int'tech Center, Katsura, Nishikyo-ku, Kyoto 615-8530, Japan
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Saki N, Jahani M, Samarbaf A, Kaydani GA, Nikakhlagh S, Kenani M, Mogehi S. Correlation Between Tympanosclerosis and Helicobacter pylori. Jundishapur J Microbiol 2015; 8:e16069. [PMID: 26568799 PMCID: PMC4640059 DOI: 10.5812/jjm.16069] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2014] [Revised: 05/12/2015] [Accepted: 06/20/2015] [Indexed: 01/27/2023] Open
Abstract
Background: Tympanosclerosis is a condition caused by calcification of tissues in the middle ear mucosa that sometimes results hearing loss. Helicobacter pylori is one of the pathological and etiologic factors in the development of tympanosclerosis. Objectives: The purpose of this study was to show the role of H. pylori in the different aspects of chronic suppurative otitis media using the polymerase chain reaction (PCR) technique. Patients and Methods: This case-control and cross-sectional study was performed on all patients with chronic otitis media, candidates for surgical operations, in 2013. They were allocated into the case group with tympanosclerosis and the control group without tympanosclerosis. During the surgical operation, biopsy was done from middle ear and the samples were studied to see if they contained H. pylori using the PCR method. Results: From a total of 19 patients with tympanosclerosis , 16 cases (84.2%) were H. pylori positive, while in the control group 15 (45.4%) cases out of the 37 cases were H. pylori positive, which showed a significant difference (P = 0.002). Age and gender of the patients, ear dryness and perforation size were not correlated with the presence or absence of H. pylori. Conclusions: There is a significant correlation between tympanosclerosis and H. pylori (P = 0.002). This correlation can single out H. pylori as a pathological factor in the development of tympanosclerosis; however, further studies are needed to prove this correlation.
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Affiliation(s)
- Nader Saki
- Department of Otolaryngology, Head and Neck Surgery, Hearing and Speech Research Centre, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Mojtaba Jahani
- Department of Otolaryngology, Hearing and Speech Research Centre, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Alireza Samarbaf
- Department of Virology, Health Research Institute, Infectious and Tropical Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Gholam Abbas Kaydani
- Department of Otolaryngology, Hearing and Speech Research Centre, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Soheila Nikakhlagh
- Department of Infectious Diseases, Health Research Institute, Infectious and Tropical Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
- Corresponding author: Soheila Nikakhlagh, Department of Infectious Diseases, Health Research Institute, Infectious and Tropical Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran. Tel: +98-6133738283, Fax: +98-6132921838, E-mail:
| | - Malek Kenani
- Department of Pathology, Health Research Institute, Infectious and Tropical Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Sasan Mogehi
- Department of Infectious Diseases, Health Research Institute, Infectious and Tropical Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
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41
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Wang J, Wang X, Tang N, Chen Y, She F. Impact of Helicobacter pylori on the growth of hepatic orthotopic graft tumors in mice. Int J Oncol 2015; 47:1416-28. [PMID: 26238296 DOI: 10.3892/ijo.2015.3107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Accepted: 05/25/2015] [Indexed: 11/05/2022] Open
Abstract
Helicobacter pylori is a well-known causative organism of chronic gastric diseases and has been found in many hepatic carcinoma samples. To explore the expression of apoptosis-related proteins and carcinoma development in H. pylori-infected livers, we utilized BALB/cAnSlac mice to establish an H. pylori-infected model by oral inoculation and orthotopic grafts of hepatic tumors by H22 cells, respectively. We found that H. pylori colonies could not be cultured from all liver and tumor samples. However, its 16S rRNA was detectable in 85.3% of livers and 66.7% of tumors in the infected mice. Inflammatory cells were observed and thinly distributed in the lobule portions of the liver, and H. pylori mainly existed in the infected hepatic sinusoids and the necrotic areas of the infected tumors. No significant difference was found in liver to body weight ratio between the infected and uninfected. Moreover, the pathological tumor difference was unremarkable between the two. The proliferating cell nuclear antigen (PCNA) and Bcl-2-associated X protein (Bax) expression in the infected tumors was significantly higher and lower, respectively, than those of the uninfected tumors. However, no significant difference in Bcl-2 (B-cell lymphoma 2) expression existed. The results indicate that H. pylori found in the livers which were infected by H. pylori oral inoculation could contribute to the infiltration of inflammatory cells in livers. Although H. pylori has no significant impact on the liver to body weight ratio or tumor Bcl-2 expression, it may upregulate PCNA expression and downregulate Bax expression, respectively. All our findings show that H. pylori may promote proliferation and inhibit apoptosis of tumor cells.
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Affiliation(s)
- Junwei Wang
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
| | - Xiaoqian Wang
- Department of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Nanhong Tang
- Department of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Yanling Chen
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
| | - Feifei She
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
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42
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Campbell LA, Rosenfeld ME. Infection and Atherosclerosis Development. Arch Med Res 2015; 46:339-50. [PMID: 26004263 PMCID: PMC4524506 DOI: 10.1016/j.arcmed.2015.05.006] [Citation(s) in RCA: 129] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2015] [Accepted: 05/12/2015] [Indexed: 01/19/2023]
Abstract
Atherosclerosis is a chronic disease hallmarked by chronic inflammation, endothelial dysfunction and lipid accumulation in the vasculature. Although lipid modification and deposition are thought to be a major source of the continuous inflammatory stimulus, a large body of evidence suggests that infectious agents may contribute to atherosclerotic processes. This could occur by either direct effects through infection of vascular cells and/or through indirect effects by induction of cytokine and acute phase reactant proteins by infection at other sites. Multiple bacterial and viral pathogens have been associated with atherosclerosis by seroepidemiological studies, identification of the infectious agent in human atherosclerotic tissue, and experimental studies demonstrating an acceleration of atherosclerosis following infection in animal models of atherosclerosis. This review will focus on those infectious agents for which biological plausibility has been demonstrated in animal models and on the challenges of proving a role of infection in human atherosclerotic disease.
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Affiliation(s)
- Lee Ann Campbell
- Department of Epidemiology, School of Public Health, Seattle, Washington, USA.
| | - Michael E Rosenfeld
- Departments of Environmental, Health and Occupational Sciences and Pathology, University of Washington, Seattle, Washington, USA
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43
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Salvatore P, Zullo A, Sommese L, Colicchio R, Picascia A, Schiano C, Mancini FP, Napoli C. Infections and cardiovascular disease: is Bartonella henselae contributing to this matter? J Med Microbiol 2015; 64:799-809. [PMID: 26066633 DOI: 10.1099/jmm.0.000099] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Cardiovascular disease is still the major cause of death worldwide despite the remarkable progress in its prevention and treatment. Endothelial progenitor cells (EPCs) have recently emerged as key players of vascular repair and regenerative medicine applied to cardiovascular disease. A large amount of effort has been put into discovering the factors that could aid or impair the number and function of EPCs, and also into characterizing these cells at the molecular level in order to facilitate their therapeutic applications in vascular disease. Interestingly, the major cardiovascular risk factors have been associated with reduced number and function of EPCs. The bacterial contribution to cardiovascular disease represents a long-standing controversy. The discovery that Bartonella henselae can infect and damage EPCs revitalizes the enduring debate about the microbiological contribution to atherosclerosis, thus allowing the hypothesis that this infection could impair the cardiovascular regenerative potential and increase the risk for cardiovascular disease. In this review, we summarize the rationale suggesting that Bartonella henselae could favour atherogenesis by infecting and damaging EPCs, thus reducing their vascular repair potential. These mechanisms suggest a novel link between communicable and non-communicable human diseases, and put forward the possibility that Bartonella henselae could enhance the susceptibility and worsen the prognosis in cardiovascular disease.
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Affiliation(s)
- Paola Salvatore
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy.,CEINGE-Advanced Biotechnologies, Naples, Italy
| | - Alberto Zullo
- CEINGE-Advanced Biotechnologies, Naples, Italy.,Department of Sciences and Technologies, University of Sannio, Benevento, Italy
| | - Linda Sommese
- U.O.C. Division of Immunohematology, Transfusion Medicine and Transplant Immunology [SIMT], Regional Reference Laboratory of Transplant Immunology [LIT], Azienda Universitaria Policlinico (AOU) and Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.,Department of Experimental Medicine, Section of Microbiology, Second University of Naples, Naples, Italy
| | - Roberta Colicchio
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy
| | - Antonietta Picascia
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy.,U.O.C. Division of Immunohematology, Transfusion Medicine and Transplant Immunology [SIMT], Regional Reference Laboratory of Transplant Immunology [LIT], Azienda Universitaria Policlinico (AOU) and Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy
| | - Concetta Schiano
- Foundation SDN, Institute of Diagnostic and Nuclear Development, IRCCS, Naples, Italy
| | | | - Claudio Napoli
- U.O.C. Division of Immunohematology, Transfusion Medicine and Transplant Immunology [SIMT], Regional Reference Laboratory of Transplant Immunology [LIT], Azienda Universitaria Policlinico (AOU) and Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.,Foundation SDN, Institute of Diagnostic and Nuclear Development, IRCCS, Naples, Italy
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Vijayvergiya R, Vadivelu R. Role of Helicobacter pylori infection in pathogenesis of atherosclerosis. World J Cardiol 2015; 7:134-143. [PMID: 25810813 PMCID: PMC4365310 DOI: 10.4330/wjc.v7.i3.134] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Accepted: 12/01/2014] [Indexed: 02/06/2023] Open
Abstract
Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and study methods along with potential confounders have yielded conflicting results. Infection triggers a chronic inflammatory state which along with other mechanisms such as dyslipidemia, hyper-homocysteinemia, hypercoagulability, impaired glucose metabolism and endothelial dysfunction, contribute in pathogenesis of atherosclerosis. Studies have shown a positive relations between Cytotoxic associated gene-A positive strains of Helicobacter pylori and vascular diseases such as coronary artery disease and stroke. Infection mediated genetic modulation is a new emerging theory in this regard. Further large scale studies on infection and atherosclerosis focusing on multiple pathogenetic mechanisms may help in refining our knowledge in this aspect.
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45
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Budzyński J, Wiśniewska J, Ciecierski M, Kędzia A. Association between Bacterial Infection and Peripheral Vascular Disease: A Review. Int J Angiol 2015; 25:3-13. [PMID: 26900306 DOI: 10.1055/s-0035-1547385] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
There are an increasing number of data showing a clinically important association between bacterial infection and peripheral artery disease (PAD). Bacteria suspected of being involved in PAD pathogenesis are: periodontal bacteria, gut microbiota, Helicobacter pylori, and Chlamydia pneumoniae. Infectious agents may be involved in the pathogenesis of atherosclerosis via activation of a systemic or local host immunological response to contamination of extravascular tissues or the vascular wall, respectively. A systemic immunological reaction may damage vascular walls in the course of autoimmunological cross-reactions between anti-pathogen antibodies and host vascular antigens (immunological mimicry), pathogen burden mechanisms (nonspecific activation of inflammatory processes in the vascular wall), and neuroendocrine-immune cross-talk. Besides activating the inflammatory pathway, bacterial infection may trigger PAD progression or exacerbation by enhancement of platelet reactivity, by a stimulatory effect on von Willebrand factor binding, factor VIII, fibrinogen, P-selectin activation, disturbances in plasma lipids, increase in oxidative stress, and resistance to insulin. Local inflammatory host reaction and induction of atherosclerotic plaque progression and/or instability result mainly from atherosclerotic plaque colonization by microorganisms. Despite these premises, the role of bacterial infection in PAD pathogenesis should still be recognized as controversial, and randomized, controlled trials are required to evaluate the outcome of periodontal or gut bacteria modification (through diet, prebiotics, and probiotics) or eradication (using antibiotics) in hard and surrogate cardiovascular endpoints.
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Affiliation(s)
- Jacek Budzyński
- Chair of Vascular and Internal Diseases, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland; Department of Vascular and Internal Diseases, Jan Biziel Hospital No. 2, Bydgoszcz, Poland
| | - Joanna Wiśniewska
- Department of Vascular and Internal Diseases, Jan Biziel Hospital No. 2, Bydgoszcz, Poland
| | - Marek Ciecierski
- Department of Vascular and Internal Diseases, Jan Biziel Hospital No. 2, Bydgoszcz, Poland
| | - Anna Kędzia
- Department of Oral Microbiology, Chair of Microbiology, Medical University, Gdańsk, Poland
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46
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Huang WS, Tseng CH, Lin CL, Tsai CH, Kao CH. Helicobacter pylori infection increases subsequent ischemic stroke risk: a nationwide population-based retrospective cohort study. QJM 2014; 107:969-75. [PMID: 24890556 DOI: 10.1093/qjmed/hcu117] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND AND PURPOSE The association of Helicobacter pylori infection (HP-I) with ischemic stroke (IS) incidence has been studied, but conflicting results have been reported. The purpose of this study was to investigate the association between chronic HP-I and the risk of acute IS by using data from the Taiwan National Health Insurance Research Database. METHODS We identified17 332 patients with HP-I and 69 328 randomly selected age- and gender-matched controls from 1 January 2000 to 31 December 2010. Both cohorts were followed up until the occurrence of IS or until censored. The Cox proportional hazards model was used for assessing the association of HP-I with IS. RESULTS Compared with the control cohort, patients diagnosed with HP-I exhibited a higher incidence rate of IS (14.8 vs. 8.45 per 1000 person years) and a hazard ratio (HR) of 1.52 (95% confidence interval [CI] = 1.40-1.65). The HRs for IS were 1.49 (1.37-1.62) in patients diagnosed with HP-I who had one admission, increasing to 2.26 (1.71-1.98) for those who had two or more admissions when adjusted for age, sex and comorbidities (P for trend < 0.0001). In addition, we observed a significantly positive association between nonembolic IS and increased admissions (P for trend < 0.0001) but negative association with embolic IS. CONCLUSION Chronic HP-I is significantly associated with an increased risk of IS, particularly nonembolic IS. Anti-HP therapy may be beneficial to IS prevention.
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Affiliation(s)
- W-S Huang
- From the Department of Neurology, China Medical University Hospital, Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, Management Office for Health Data, China Medical University Hospital and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan From the Department of Neurology, China Medical University Hospital, Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, Management Office for Health Data, China Medical University Hospital and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
| | - C-H Tseng
- From the Department of Neurology, China Medical University Hospital, Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, Management Office for Health Data, China Medical University Hospital and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan From the Department of Neurology, China Medical University Hospital, Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, Management Office for Health Data, China Medical University Hospital and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
| | - C-L Lin
- From the Department of Neurology, China Medical University Hospital, Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, Management Office for Health Data, China Medical University Hospital and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
| | - C-H Tsai
- From the Department of Neurology, China Medical University Hospital, Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, Management Office for Health Data, China Medical University Hospital and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan From the Department of Neurology, China Medical University Hospital, Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, Management Office for Health Data, China Medical University Hospital and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
| | - C-H Kao
- From the Department of Neurology, China Medical University Hospital, Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, Management Office for Health Data, China Medical University Hospital and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan From the Department of Neurology, China Medical University Hospital, Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, Management Office for Health Data, China Medical University Hospital and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
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47
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He C, Yang Z, Lu NH. Helicobacter pylori-an infectious risk factor for atherosclerosis? J Atheroscler Thromb 2014; 21:1229-42. [PMID: 25342566 DOI: 10.5551/jat.25775] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
Accumulating evidence implicates Helicobacter pylori (H. pylori) infection in the pathogenesis of certain diseases localized outside the stomach, particularly those characterized by persistent and low-grade systematic inflammation. Recently, the role of H. pylori infection in the development of atherosclerosis and its clinical complications has received attention. Atherosclerosis is a high-cost disease, and acute events resulting from this condition rank first among morbidity and mortality statistics in most industrialized countries. Atherosclerosis is a multifactorial disorder, and traditional risk factors explain only 50% of its etiology. Therefore, identifying new risk factors for atherosclerosis is necessary. Serological studies indicate that chronic H. pylori infection, especially that with more virulent strains, may predispose patients to the onset of atherosclerosis and related adverse clinical events, and PCR studies have detected H. pylori DNA in atherosclerotic plaques, although this finding remains controversial. If this association were to be confirmed, its importance to public health would be substantial, as the eradication of H. pylori is more straightforward and less costly than the long-term treatment of other risk factors. This review investigates the potential relationship between H. pylori infection and atherosclerosis from both epidemiological and pathogenic perspectives and characterizes the potential mechanisms underlying this correlation.
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Affiliation(s)
- Cong He
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University
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48
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Wong F, Rayner-Hartley E, Byrne MF. Extraintestinal manifestations of Helicobacter pylori: A concise review. World J Gastroenterol 2014; 20:11950-11961. [PMID: 25232230 PMCID: PMC4161781 DOI: 10.3748/wjg.v20.i34.11950] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 01/28/2014] [Accepted: 05/05/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection has been clearly linked to peptic ulcer disease and some gastrointestinal malignancies. Increasing evidence demonstrates possible associations to disease states in other organ systems, known as the extraintestinal manifestations of H. pylori. Different conditions associated with H. pylori infection include those from hematologic, cardiopulmonary, metabolic, neurologic, and dermatologic systems. The aim of this article is to provide a concise review of the evidence that supports or refutes the associations of H. pylori and its proposed extraintestinal manifestations. Based on data from the literature, PUD, mucosal associated lymphoid tumors lymphoma, and gastric adenocarcinoma has well-established links. Current evidence most supports extraintestinal manifestations with H. pylori in immune thrombocytopenic purpura, iron deficiency anemia, urticaria, Parkinson’s, migraines and rosacea; however, there is still plausible link with other diseases that requires further research.
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Nisha KJ, Nandakumar K, Shenoy KT, Janam P. Periodontal disease and Helicobacter pylori infection: a community-based study using serology and rapid urease test. ACTA ACUST UNITED AC 2014; 7:37-45. [PMID: 25175565 DOI: 10.1111/jicd.12122] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2013] [Accepted: 07/02/2014] [Indexed: 12/29/2022]
Abstract
AIMS The aims of the present study were to assess the prevalence of periodontal disease and Helicobacter pylori (H. pylori) infection and their associations within a predefined Indian population. METHODS A community-based cross-sectional study of 500 selected individuals using a questionnaire, oral examination, rapid urease testing of dental plaque, and serological examination for immunoglobulin G antibody to H. pylori was carried out. RESULTS Periodontal disease and H. pylori infection were prevalent in more than 50% of the population. Age, smoking, and diabetic status of the individuals were risk factors for periodontal disease after multivariate analysis, and a lack of proper sewage and waste disposal facilities were found to increase the risk of H. pylori infection. Although there was no association between periodontal disease and H. pylori seropositivity in the community, a highly-significant association was found between periodontal disease and colonization of H. pylori in dental plaque. CONCLUSIONS Because periodontal disease is associated with the increased colonization of H. pylori, new treatment modalities, such as plaque control measures, should be employed for the complete management of H. pylori-associated gastric disease.
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Sikorski K, Wesoly J, Bluyssen HAR. Data mining of atherosclerotic plaque transcriptomes predicts STAT1-dependent inflammatory signal integration in vascular disease. Int J Mol Sci 2014; 15:14313-31. [PMID: 25196434 PMCID: PMC4159852 DOI: 10.3390/ijms150814313] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Revised: 07/29/2014] [Accepted: 08/01/2014] [Indexed: 01/02/2023] Open
Abstract
Atherosclerotic plaque development involves multiple extra- and intra-cellular signals engaging cells from the immune system and from the vasculature. Pro-inflammatory pathways activated by interferon gamma (IFNγ) and toll-like receptor 4 (TLR4) ligands are profoundly involved in plaque formation and have been shown to involve cross-talk in all atheroma-interacting cell types leading to increased activation of signal transducer and activator of transcription-1 (STAT1) and elevated expression of pro-inflammatory mediators. Here we demonstrate that in Gene Expression Omnibus repository (GEO) deposited microarray datasets, obtained from human coronary and carotid atherosclerotic plaques, a significant increase in expression of pro-inflammatory and immunomodulatory genes can be detected. Moreover, increased expression of multiple chemokines, adhesion molecules and matrix-remodeling molecules was commonly detected in both plaque types and correlated with the presence of putative STAT1 binding sites in their promoters, suggesting strong involvement of STAT1 in plaque development. We also provide evidence to suggest that STAT1-nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) or STAT1-interferon-regulated factor (IRF) regulatory modules are over-represented in the promoters of these inflammatory genes, which points to a possible contribution of IFNγ and TLR4 cross-talk in the process of atherogenesis. Finally, a subset of these genes encodes for secreted proteins that could serve as a basis of a non-invasive diagnostic assay. The results of our in silico analysis in vitro provide potential evidence that STAT1-dependent IFNγ-TLR4 cross-talk plays a crucial role in coronary and carotid artery plaque development and identifies a STAT1-dependent gene signature that could represent a novel diagnostic tool to monitor and diagnose plaque progression in human atherosclerosis.
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Affiliation(s)
- Krzysztof Sikorski
- Department of Human Molecular Genetics, Adam Mickiewicz University in Poznan, Poznan 61-614, Poland.
| | - Joanna Wesoly
- Laboratory of High-Throughput Technologies, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Umultowska 89, Poznan 61-614, Poland.
| | - Hans A R Bluyssen
- Department of Human Molecular Genetics, Adam Mickiewicz University in Poznan, Poznan 61-614, Poland.
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