Despite recent progress, challenges with small-diameter vascular grafts, including mechanical strength, intimal hyperplasia, thrombosis, and poor endothelialization, remain unresolved. The present study reports a novel bilayer vascular graft designed to mimic the anatomical features of small-diameter blood vessels. The electrospun graft consists of a dense micro/nanofibrous inner layer of cardiac extracellular matrix (cECM), polycaprolactone (PCL) loaded with heparin (P-cECM-H), and a super porous and micro-fibrous PCL outer layer. Liquid chromatography-mass spectrometry (LC-MS/MS) proteome analysis of the cECM revealed that it is enriched with several bioactive proteins related to angiogenesis, wound regeneration, cell migration, etc. The porosities of the two layers are tailored according to endothelial and smooth muscle cell biology. The graft exhibited excellent mechanical properties, and the heparinized P-cECM inner layer improved hemocompatibility and anticoagulation efficacy. A significant increase in endothelial cell proliferation was noted in the P-cECM-H group after 7 days compared with the control group (p < 0.05). The bilayer graft maintained 100 % patency after 10 weeks of rat abdominal aorta implantation. Histological evaluation revealed smooth muscle cell infiltration inside the highly porous outer layer and neointima regeneration in the inner layer with a complete endothelial lining. RNA sequencing (RNA-Seq) analysis further confirmed smooth muscle formation and endothelial layer formation. The gene expression data also suggested that the hypoxia-inducible factor-1 (HIF-) and vascular endothelial growth factor (VEGF) signaling pathways are involved in endothelial layer remodeling. These promising results indicate that cECM could be a key material for vascular tissue regeneration.

Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid accumulation and inflammation. Macrophage phenotypic transformation plays a critical role in AS progression. Aryl hydrocarbon receptor (AhR) has been proved to regulate the phenotype of macrophages. This study investigates the role and molecular mechanism of AhR activation by its endogenous ligand, 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) attenuates AS.

We employed Western blotting to analyze the expression of AhR, NF-κB, and lipocalin-2 (LCN2). Flow cytometry and immunofluorescence staining were used to assess the phenotype of macrophages. Plaque progression was evaluated using pathological staining. Transcriptome sequencing was utilized to explore the potential mechanism by which AhR promotes macrophage phenotypic transformation. CUT&Tag-qPCR and lentivirus infection confirmed that the AhR/NF-κB/LCN2 pathway regulates macrophage polarization.

Activation of AhR by ITE reduced plaque area and inhibited lipid deposition. ITE significantly increased the number of M2-like macrophages both in vivo and in vitro. Transcriptome sequencing identified LCN2 as a key target for AhR-mediated macrophage M2-like polarization. Furthermore, AhR activation suppressed the NF-κB/LCN2 pathway.

Our findings reveal that AhR promotes the macrophages to exhibit M2-like characteristics to attenuate AS by inhibiting the NF-κB/LCN2 pathway. These results suggest that AhR may serve as a novel therapeutic target for AS.

Atherosclerosis is induced by lipid accumulation, inflammation, and endothelial dysfunction, and is the leading cause of death from cardiovascular disease worldwide. The P2Y6 receptor can be activated by the extracellular release of UDP. The evidence from the last decade has highlighted its critical therapeutic effect in atherosclerosis, yet with unclear mechanisms. This review introduced the P2Y6 receptor in atherosclerosis, and its mechanisms of atherosclerosis-promoting in macrophages, endothelial cells, and vascular smooth muscle cells. Finally, we discussed the development and potential of P2Y6 receptor antagonists in treating atherosclerosis.

Atherosclerosis is the leading cause of cardiovascular disease-related morbidity and mortality. The traditional Chinese medicine Qingre Sanjie Formula (QRSJF), composed of Prunellae Spica, Sargassum, Fritillariae Thunbergii Bulbus, Leonuri Herba, and Forsythiae Fructus, has shown efficacy in treating cardiovascular diseases, although its mechanisms are unclear.

This study aimed to explore the protective effects of QRSJF against atherosclerosis and the mechanisms involved.

The composition of QRSJF was analyzed using Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry. An 8-week high-fat diet (HFD)-induced atherosclerosis model was established in ApoE-/- mice. Following model induction, mice received 12 weeks of QRSJF treatment at high- and low doses (3.16 and 1.58 g drug/kg/day, respectively) via oral gavage, while simvastatin (2.6 mg/kg/day) as the positive control. Various techniques, including biochemical assays, vascular ultrasonography, histopathology, untargeted metabolomics, and molecular biology techniques were utilized to evaluate therapeutic effects. The underlying mechanism was investigated in vitro using free fatty acids -induced HepG2 cells.

Both low- and high-dose QRSJF effectively attenuated dyslipidemia and decreased serum inflammatory cytokine levels in HFD-fed ApoE-/- mice. In addition, QRSJF alleviated atherosclerotic plaque formation, reduced arterial narrowing, and enhanced plaque stability. Plasma and liver metabolomic analyses further identified that ABC (ATP binding cassette) subfamily transporters and bile acid metabolism as key pathways through which QRSJF ameliorates atherosclerosis. QRSJF also alleviated liver lipid accumulation and increased the expression of liver proteins, including scavenger receptor class B type 1, low-density lipoprotein receptor, ABC subfamily A member 1, cholesterol 7α-hydroxylase (CYP7A1), ABC transporter G5/G8 (ABCG5/G8), bile salt output pump, and liver X receptor alpha (LXR-α). In vitro, QRSJF activated LXR-α expression in HepG2 cells, thereby enhancing the expression of the downstream targets, CYP7A1 and ABCG5/8, and reducing free fatty acid-induced lipid accumulation. Notably, the beneficial effects of QRSJF were abrogated by the LXR-α inhibitor GSK2033.

QRSJF improves dyslipidemia and reduces atherosclerotic plaque in ApoE-/- mice by activating the LXR-α/ABCG5/G8 pathway. This facilitates cholesterol transport to the liver and promotes bile acid synthesis and cholesterol excretion into the bile and intestine, thereby exerting anti-atherosclerotic effects.

Coronary heart disease (CHD) represents a significant cardiovascular condition, with its occurrence increasing as a result of alterations in lifestyle and dietary habits. Semen Ziziphi Spinosae (SZS) is commonly utilized for the management of disorders associated with the nervous system, including conditions like depression and insomnia. Recent research has revealed its potential therapeutic properties for cardiovascular issues. Nevertheless, there exists a limited amount of research addressing the mechanisms involved.

This research seeks to explore the protective effects that SZS has on cardiac tissue, specifically within the framework of CHD. By conducting this investigation, the study aims to uncover the various mechanisms that play a role in these protective effects. This understanding could yield significant insights into how SZS may result in the preservation and enhancement of cardiac health in patients affected by CHD.

The study innovatively combines multiple advanced techniques. It first integrates UPLC-Q-TOF/MS analysis and network pharmacology to identify SZS components. In vitro experiments were conducted using H9c2 rat cardiomyocytes, and in vivo experiments used a CHD model in SD rats. Multiple assays were performed for multi - level and multi - dimensional validation.

In the initial stage, the primary components of SZS and their possible mechanisms for combating CHD were examined through UPLC-Q-TOF/MS analysis in conjunction with network pharmacology approaches. For the in vitro investigation, an ischemia-hypoxia model was established utilizing H9c2 rat cardiomyocytes. The CCK-8 assay was used to assess myocardial injury markers. TUNEL staining and Western blot techniques were employed to confirm the impact of SZS treatment on apoptosis in H9c2 cells. The expression levels of proteins associated with the AMPK/SIRT1/PGC-1α signaling pathway were measured using RT-qPCR and Western blotting, and the results were validated with the AMPK inhibitor, compound C. In the in vivo segment, a model of coronary heart disease (CHD) in SD rats was established through the administration of a high-fat emulsion diet combined with pituitrin injections. Cardiac function in the rats was evaluated through electrocardiograms and echocardiograms. Pathological changes in the heart were observed utilizing TTC and H&E staining. Kits were implemented to measure the serum biochemical indicators in the rats.RT - qPCR and Western blotting were employed to measure the expression levels of proteins related to the AMPK/SIRT1/PGC - 1α signaling pathway.

The study identified 67 in vitro components, 27 blood - absorbed components, and 12 metabolic components of SZS. Network pharmacology analysis suggested the AMPK/SIRT1/PGC - 1α signaling pathway as a key mechanism. In vitro and in vivo experiments showed that SZS increased cell viability, reduced apoptosis, and activated the AMPK/SIRT1/PGC - 1α signaling pathway. Inhibiting AMPK abolished SZS's effects. SZS also improved cardiac function and reduced myocardial damage in rats with CHD.

This study for the first time highlights that Semen Ziziphi Spinosae plays a beneficial role in cardiovascular health by activating the AMPK/SIRT1/PGC-1α signaling pathway and reducing apoptosis in cardiomyocytes. These findings support its potential application in the treatment of CHD and other cardiac conditions.

Vascular aging is a key driver of age-related cardiovascular and metabolic diseases, with endothelial dysfunction and senescence as a central mechanism. In our recent study, we observed elevated ADAM10 protein levels in senescent endothelial cells, which worsened endothelial dysfunction and senescence. However, the regulatory mechanisms controlling ADAM10 expression are poorly understood. In this study, we show that ADAM10 undergoes post-transcriptional modification in senescent human umbilical vein endothelial cells (HUVECs), with the E3 ubiquitin ligase MARCHF8 predicted to facilitate its ubiquitination-dependent degradation. We also found that MARCHF8 expression was significantly reduced in senescent HUVECs. Knockdown of MARCHF8 in young HUVECs induced endothelial senescence and impaired key endothelial functions, including migration, proliferation, angiogenesis, and nitric oxide production. Conversely, overexpression of MARCHF8 in senescent HUVECs ameliorated senescence-associated dysfunctions. RNA sequencing analysis revealed that MARCHF8 knockdown disrupted pathways linked to cell senescence and atherosclerosis. In vivo, MARCHF8 overexpression in high-fat diet-fed apoE-/- mice reduced plasma interleukin-6 levels and attenuated atherosclerosis progression. Additionally, miR-34a-5p upregulation in senescence inhibited MARCHF8 expression, compromising its protective effects in delaying endothelial senescence. Collectively, these findings reveal a novel miR-34a-5p/MARCHF8/ADAM10 axis in vascular endothelial senescence, positioning MARCHF8 as a potential biomarker and therapeutic target for vascular aging and related diseases.

Cardiovascular disease is one of the leading causes of death worldwide. Even while receiving adequate pharmacological treatment for their hypertension, people are nonetheless at greater risk for cardiovascular disease. There is growing evidence that the gut microbiota may have major positive and negative effects on blood pressure and illnesses related with it as more study into this topic is conducted. Trimethylamine n-oxide (TMAO) and short-chain fatty acids (SCFA) are two major by-products of the gut microbiota. TMAO is involved in the formation of other coronary artery diseases, including atherosclerosis and hypertension, while SCFAs play an important role in controlling blood pressure. Numerous investigations have confirmed the established link between dietary salt intake and hypertension. Reducing sodium in the diet is linked to lower rates of cardiovascular disease morbidity and mortality as well as lower rates of blood pressure and hypertension. In both human and animal research, high salt diets increase local and systemic tissue inflammation and compromise gut architecture. Given that the gut microbiota constantly interacts with the immune system and is required for the correct maturation of immune cells, it is scientifically conceivable that it mediates the inflammatory response. This review highlights the therapeutic possibilities for focusing on intestinal microbiomes as well as the potential functions of the gut microbiota and its metabolites in the development of hypertension.

Excessive hepatic lipid accumulation is the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), yet its underlying mechanisms still not fully understood. In this study, we identified RNA binding motif protein 39 (Rbm39) as a key modulator of hepatic lipid homeostasis during MASLD progression. To establish in vivo MASLD model, mice were fed either a high-fat diet (HFD) or a Gubra-Amylin NASH (GAN) diet. We employed adeno-associated virus to manipulate Rbm39 expression levels to assess its role in MASLD. Transcriptome analysis was conducted to pinpoint the genes targeted by Rbm39. Western blot, RT-PCR, dual-luciferase reporter gene assays, and alternative splicing analysis were utilized to delve into the molecular mechanisms. Our results showed that Rbm39 expression was notably decreased in the livers of MASLD mice. Knockdown of hepatic Rbm39 aggravated HFD-induced hepatic steatosis and GAN diet-induced MASH, along with a notable decrease in serum lipid levels. Conversely, overexpression of Rbm39 attenuated MASLD development and progression. RNA sequencing data analysis indicated that Rbm39 regulated the expression of apolipoprotein B (Apob) and fatty acid-binding protein 4 (Fabp4), both of which are crucial for lipid transport. Mechanistically, Rbm39 enhanced the transcription of Apob by upregulating hepatocyte nuclear factor 4α (Hnf4α), while it suppressed Fabp4 transcription by regulating alternative splicing of hypoxia inducible factor-1α (Hif-1α). These findings highlight the pivotal role of Rbm39 in maintaining hepatic lipid homeostasis and suggest its potential as a therapeutic target for MASLD.

Cardiovascular diseases caused by atherosclerosis (AS) are the leading causes of disability and death worldwide. Apolipoprotein B (ApoB), the core protein of low-density lipoproteins, is a major contributor to cardiovascular disease-related morbidity and mortality, with apolipoprotein B (ApoB) playing a critical role in its pathogenesis. However, no bibliometric studies on the involvement of ApoB in AS have been published. This study aimed to conduct a comprehensive bibliometric analysis to explore the current and future trends regarding the role of ApoB in AS.

Utilizing the Web of Science Core Collection, a thorough search was conducted for ApoB in AS-related papers related to research on ApoB in the field of AS during 1991-2023. The analysis focused on annual publication trends, leading countries/regions and institutions, influential authors, journal and key journals. CiteSpace and VOSviewer were employed to visualize reference co-citations, and keyword co-occurrences, offering insights into the research landscape and emerging trends.

This bibliometric analysis employed network diagrams for cluster analysis of a total of 2105 articles and reviews, evidencing a discernible upward trend in annual publication volume. This corpus of research emanates from 76 countries/regions and 2343 organizations, illustrating the widespread international engagement in ApoB-related AS studies. Notably, the United States and the University of California emerge as the most prolific contributors, which underscores their pivotal roles in advancing this research domain. The thematic investigation has increasingly focused on elucidating the mechanistic involvement of ApoB in atherosclerosis, its potential as a diagnostic biomarker, and its implications for therapeutic strategies.

This bibliometric analysis provides the first comprehensive perspective on the evolving promise of ApoB in AS-related research, emphasizing the importance of this molecule in opening up new diagnostic and therapeutic avenues. This study emphasizes the need for continued research and interdisciplinary efforts to strengthen the fight against AS. Furthermore, it emphasizes the critical role of international collaboration and interdisciplinary exploration in leveraging new insights to achieve clinical breakthroughs, thereby addressing the complexities of AS by focusing on ApoB.

This review presents an overview of the regulation, function, disease-relevance and pharmacological regulation of the critical endothelial transcription factors KLF2/4 in vasculature. The regulatory mechanisms of KLF2/4 expression and activity in vascular endothelium in response to hemodynamic forces and biochemical stimuli are depicted. The functional effects mediated by direct or indirect target genes of KLF2/4 in endothelial cells are systematically summarized. The contributory roles that dysregulated KLF2/4 play in relevant cardiovascular pathologies, such as atherosclerotic vascular lesions, pulmonary arterial hypertension and vascular complications of diabetes were reviewed. Moreover, this review also discusses the pharmacological regulation of KLF2/4 by drugs used in clinics and therapeutic possibility by directly targeting these two transcription factors for treating atherosclerotic cardiovascular diseases. Finally, prospective opinions on the gaps in disclosing novel vascular function mediated by KLF2/4 and future research needs are expressed.

Chronic widespread pain (CWP) is prevalent and associated with reduced life expectancy. Cardiovascular disease is one possible mechanism for this. The purpose of this study was to examine the association of CWP with arterial stiffness and carotid plaque measured using ultrasound to determine if shared environmental or genetic factors might account for any observed association. Around 3000 participants from the TwinsUK with CWP information and measures of carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and plaque were considered. The relationship between CWP and cfPWV, cIMT, and plaque was determined. UK Biobank data were used to replicate the association. Cholesky decomposition and multivariate pathway twin models were examined. Using a 2-sample Mendelian randomisation approach, the causal association between CWP and coronary artery disease was assessed. TwinsUK participants demonstrated a significant association between CWP and increased cfPWV consistent with arterial stiffening (OR = 1.35, P -value = 0.012), as well as the presence of carotid plaque (OR = 1.45, P -value = 0.8e-5). The twin modelling showed a common latent component and pathway underlying CWP, cfPWV, and carotid plaque, with genetic factors accounting for 68% and 90% of the latent factor variation, respectively. The 2-sample MR revealed a potential causal association between CWP and coronary artery disease. This study found that those with CWP have increased the risk of arterial stiffness and atherosclerosis and suggests that CWP leads to an increased risk of cardiovascular disease through genetic factors.

As a novel indicator reflecting metabolic status and visceral adiposity distribution, the cardiometabolic index (CMI) has gained attention in cardiovascular risk stratification. This investigation employed optical coherence tomography (OCT) to examine potential associations between CMI and vulnerable plaque, as well as the role of inflammation.

This study conducted a cross-sectional analysis of 270 acute coronary syndrome (ACS) patients who had OCT imaging evaluation. Patients were categorized based on CMI tertiles, with CMI calculated using the formula [waist (cm)/height (cm)]×[triglycerides (mmol/L)/HDL-C (mmol/L)]. OCT was used to assess plaque events in culprit lesions and plaque components in non-culprit lesions, and inflammatory markers were measured. A mediation analysis framework was implemented to investigate inflammatory pathways in CMI-vulnerable plaque relationships.

CMI tertiles were linked to vulnerable plaque traits: thin-cap fibroatheromas (TCFA), macrophages (Tertiles1 vs. Tertiles2 vs. Tertiles3, TCFA: 10.0% vs. 20.0% vs. 26.7%, P = 0.016; macrophages: 17.8% vs. 28.9% vs. 36.7%, P = 0.019). Multivariate regression demonstrated CMI elevation independently predicted a higher prevalence of TCFA (OR:1.40, 95%CI: 1.25-2.89, P = 0.003), more macrophage infiltration (OR:1.61, 95% CI:1.09-2.37, P = 0.017), reduced FCT (β:-30.65, 95% CI:-50.72-10.57, P = 0.003), and enlarged maximum lipid arc (β:20.78, 95% CI:6.55-35.01, P = 0.004). Moreover, CMI was positively related to hsCRP, WBC, and neutrophils. Mediation analysis revealed that hsCRP mediated about 17.0% of the association between CMI and minimum FCT [Indirect effect=-5.21, 95% CI=(-12.70, -1.27), P = 0.016].

CMI is a key forecaster of vulnerable plaque in patients with ACS. Systemic inflammation is associated with the relationship between CMI and vulnerable plaque features, suggesting a potential mechanistic link.

Atherosclerosis is the primary driver of cardiovascular and cerebral vascular diseases globally. Atherosclerotic plaques have been detected in multiple arterial locations, such as the aorta, carotids, and coronaries. However, it remains uncertain if there are variations in susceptibility and association among arteries of different calibers. Utilizing a spontaneous rhesus monkey model of metabolic syndrome (MetS), we assessed the susceptibility of atherosclerosis among the radial artery, femoral artery, and carotid artery and their correlation with coronary heart disease (CHD). The development of atherosclerosis in the three arteries mentioned above was evaluated by Intima-media thickness (IMT) and plaques using echo imaging over 6 years in a cohort of elderly monkeys with metabolic disorders. Coronary artery stenosis was assessed by coronary flow reserve (CFR) simultaneously. The diagnosis was further confirmed by histopathological examination, and RNA sequencing was employed to probe the transcriptional underpinnings of atherosclerotic development. The spontaneous development of atherosclerosis was observed in elderly monkeys, and the incidence of atherosclerosis was increased by three times in the MetS monkeys compared to the age-matched control group. During the 6-year follow-up, there was a notable increase in the IMT across all three arteries, with the radial artery showing the most pronounced thickening. Moreover, only the radial IMT correlated with CFR, suggesting its potential as a non-invasive diagnostic indicator for CHD. Histopathology confirmed the findings by echo imaging and identified different extracellular matrix (ECM) remodeling patterns in the arteries. In addition, transcriptomic analysis revealed that ECM remodeling and inflammation-related pathways were significantly upregulated in radial atherosclerotic samples, multiple inflammatory pathways were upregulated in the femoral lesion samples, and the carotid samples failed to enrich any pathways due to a lack of differentially expressed genes compared to the control samples. Non-human primates, which share extensive genetic and physiological similarities with humans, develop atherosclerosis spontaneously. This provides an invaluable platform for investigating the intricate mechanisms of arterial disease and evaluating potential treatments. Using the monkey model, we identified the radial artery as a sensitive indicator for assessing the occurrence and progression of atherosclerosis and coronary stenosis.

Cardiovascular diseases including atherosclerosis and heart failure, arise from the intricate interplay of metabolic, immune, and neural dysregulation within vascular and cardiac tissues: This review focuses on integrating recent advances in metabolic and immune crosstalk of the cardiac vasculature that affects cardiometabolic health and disease progression. Coronary and lymphatic endothelial cells regulate cardiac metabolism, and their dysfunction is linked to cardiovascular diseases. Lymphatics maintain tissue homeostasis, including clearing metabolic waste, lipids, and immune cells, and their maladaptation in metabolic diseases worsens outcomes. Altered vascular endothelial metabolism in heart failure drives immune-mediated inflammation, fibrosis, and adverse cardiac remodeling. Concurrently, artery tertiary lymphoid organs formed in the adventitia of advanced atherosclerotic arteries, serve as pivotal neuroimmune hubs, coordinating local immunity through T and B cell activation and neurovascular signaling via artery-brain circuits. T cells within plaques and artery tertiary lymphoid organs undergo clonal expansion as a result of peripheral tolerance breakdown, with proinflammatory CD4+ and CD8+ subsets amplifying atherosclerosis, effects further shaped by systemic immune activation. Therapeutic strategies targeting endothelial cell metabolism, lymphatic dysfunction, neuroimmune crosstalk, and T cell plasticity hold promise for integrated cardiovascular disease management.

Cellular senescence is a complex biological process with a dual role in tissue homeostasis and aging-related pathologies. Accumulation of senescent cells promotes chronic inflammation, tissue dysfunction, age-related diseases, and tumor suppression. Recent advancements in immunotherapy have positioned T cell-based approaches as precision tools for the targeted clearance of senescent cells, offering a novel avenue for anti-aging interventions. This review explores the molecular mechanisms underlying cellular senescence, focusing on its immunogenic features and interactions with T cells, including T-cell activation, antigen recognition, modulation of tumor microenvironment (TME), and immune evasion strategies. Innovations such as chimeric antigen receptor (CAR)-T cells, immune checkpoint therapies, and SASP-neutralizing approaches are highlighted as breakthrough strategies for enhancing senescent cell eradication. The integration of multi-omics and artificial intelligence is further catalyzing the development of personalized therapies to amplify immune surveillance and tissue rejuvenation. Clinically, T cell-based interventions hold promise for mitigating age-related pathologies and extending healthspan, yet challenges remain in optimizing target specificity, countering immunosuppressive niches, and overcoming immune senescence in aging populations. This review synthesizes current advances and challenges, highlighting the potential of T cell immunotherapy as a cornerstone of anti-aging medicine and emphasizing the need for interdisciplinary innovation to translate preclinical findings into transformative therapies for aging and age-related diseases.

The notion of clonal cell populations in human atherosclerosis has been suggested but not demonstrated. Somatic mutations are used to define cellular clones in tumors. Here, we characterized the mutational landscape of human carotid plaques through whole-exome sequencing to explore the presence of clonal cell populations. Somatic mutations were identified in 12 of 13 investigated plaques, while no mutations were detected in 11 non-atherosclerotic arteries. Mutated clones often constituted over 10% of the sample cell population, with genes related to the contractile apparatus enriched for mutations. In carriers of clonal hematopoiesis of indeterminate potential (CHIP), hematopoietic clones had infiltrated the plaque tissue and constituted substantial fractions of the plaque cell population alongside locally expanded clones. Our findings establish somatic mutations as a common feature of human atherosclerosis and demonstrate the existence of mutated clones expanding locally, as well as CHIP clones invading from the circulation. While our data do not support plaque monoclonality, we observed a pattern suggesting the coexistence of multiple mutated clones of considerable size spanning different regions of plaques. Mutated clones are likely to be relevant to disease development, and somatic mutations will serve as a convenient tool to uncover novel pathological processes of atherosclerosis in future studies.

Atherosclerosis, a major cause of global mortality, involves the transformation of macrophages into foam cells, which is a key pathological process. This study aims to elucidate the molecular mechanisms that contribute to foam cell formation and the progression of atherosclerosis.

We performed a comprehensive bioinformatics analysis of transcriptome data to identify differentially expressed genes (DEGs) associated with atherosclerosis. Using the human acute monocytic leukemia cell line THP-1, we established in vitro models of macrophages and foam cells to simulate the atherosclerotic microenvironment. Functional studies were conducted using siRNA-mediated knockdown, real-time PCR, Western blotting, and immunofluorescence imaging. Our results showed that ATP8B2 was significantly down-regulated in atherosclerotic foam cells. The downregulation of ATP8B2 led to impaired lysosomal membrane fusion, evidenced by an increase in CD63-positive compartments without a change in CD63 protein levels. Additionally, under starvation conditions, there was a significant accumulation of autophagosomes, indicating a defect in the autophagy-lysosomal pathway.

This study, for the first time, demonstrates that the downregulation of ATP8B2 exacerbates atherosclerosis by disrupting lysosomal membrane fusion, leading to lipid accumulation and foam cell formation. These findings provide novel insights into the pathogenesis of atherosclerosis and suggest that ATP8B2 could be a potential therapeutic target for the prevention or treatment of this disease.

Moonlighting proteins are multifunctional proteins widely present in organisms, playing crucial roles in various physiological activities. Drawing inspiration from the moonlight proteins, we developed a cerium (Ce)-based nanozyme CF, featuring multiple enzymatic activities along with robust cargo-loading and transport capabilities. The CF was synthesized through a one-step assembly between Ce3+ and a phosphorylated amino acid derivative, achieving high biostability through a simple heat treatment. The nanozyme possesses both superoxide dismutase (SOD) and catalase (CAT) activities, enabling scavenging of reactive oxygen species (ROS) and modulation of inflammation by inhibiting NF-κB pathway activation. Besides its enzymatic activities, CF can also serve as a versatile nanocarrier for various cargoes through one-pot co-assembly. Herein, the CF-based nanoassembly loaded with a near infrared fluorescent dye was demonstrated to work well for the diagnosis of atherosclerotic plaques. The nanoassembly co-assembled with probucol exhibited superior ROS-scavenging and anti-inflammatory effects compared to either CF nanozyme or probucol, attributed to the synergy of the nanozyme and the drug, thus facilitating a highly efficient treatment of atherosclerosis. This work introduces a novel Ce-based nanozyme with multifunctional properties, providing a promising approach to endow nanozymes with moonlighting protein-like characteristics, thereby enhancing their functional capabilities and broadening their application potential in various fields.

Atherosclerosis, a chronic inflammatory disorder and leading cause of cardiovascular disease, is characterized by macrophage-derived inflammation and foam cell formation. Emerging evidence suggests that metabolic reprogramming of macrophages represents a promising therapeutic approach for atherosclerosis management. In this study, the therapeutic potential of wogonin, a bioactive flavonoid isolated from Scutellaria baicalensis, in modulating macrophage metabolism and attenuating atherogenesis is investigated. Wogonin reduces lesion size and plaque vulnerability, accompanied by a reduction in foam cell formation and inflammation. Mechanistically, wogonin reprogrammes macrophage metabolism from glycolysis to fatty acid oxidation (FAO) by activating the PPARα-CPT1α pathway and acts as a mitochondrial protector by activating PPARα. Wogonin also promotes the KLF11 expression and KLF11 knockout exacerbated atherosclerosis and abolishes the inhibitory effect of wogonin on glycolysis and atherosclerosis. KLF11 forms a transcriptional complex with PPARα and YAP1, serving both as a brake on PPARα-YAP1-mediated glycolysis and a transcriptional activator of ABCA1/G1. Collectively, wogonin reprograms macrophage metabolism from glycolysis to FAO through activation of the PPARα-KLF11-YAP1 pathway, thereby reducing inflammation and foam cell formation, ultimately attenuating atherogenesis.

Hyperhomocysteinemia (HHy) can lead to vascular endothelial cell dysfunction, progressive inflammation and lipid metabolism disorder, which finally result in the onset and development of atherosclerosis, a major contributor to cardiovascular diseases. Given the complexity of pathological process, treatments based on a single target often showed limited therapeutic efficacy against AS. Thus, developing nanodrug for enhanced multi-targets therapy is promising. In this study, we constructed a dual-targeting nanodrug (HA-ML@ES NPs) co-loaded with Shikonin (SKN) and Evolocumab (Evol). In vitro results showed that HA-ML@ES NPs could simultaneously target dysfunctional endothelial cell and inflammatory macrophage through the interaction between HA and CD44. In vivo assay indicated that HA-ML@ES NPs with long circulation and plaque accumulation efficiently attenuate endothelial cell dysfunction by inhibiting glycolysis and restore cholesterol flow homeostasis in macrophage by reprogramming macrophage phenotype, which finally attenuated the development of atherosclerosis. Collectively, these results present a highly promising dual-cell therapeutic approach based on HA-ML@ES NPs for the management of early atherosclerosis.

Chitooligosaccharides (COSs), degraded products of chitosan or chitin, are attracting growing interest owing to their low degree of polymerization (DP), high solubility, and prominent anti-inflammatory activity. However, the correlation between their structure and anti-inflammatory activities still needs to be explored. In this study, we use LPS-stimulated RAW 264.7 macrophages as an inflammatory model to systematically evaluate COS1-7 for their effects on inflammatory mediators and NF-κB signaling pathways. The results of Griess assay, ELISA, and real-time quantitative PCR show that COSs can inhibit the expression of NO, iNOS, and pro-inflammatory cytokines (IL-6, TNF-α, MCP-1 and IL-1β), thereby attenuating inflammatory signaling. Notably, chitohexaose (COS6) exhibits the most significant anti-inflammatory effect, reducing the mRNA levels of LPS-induced iNOS, IL-6, and IL-1β and the production of IL-6 and TNF-α by more than 50%. Transcriptome, western blotting, and real-time quantitative PCR analysis reveal that COSs can inhibit the activation of the NF-κB signal pathway by down-regulating TLR2 levels. Additionally, molecular docking confirms that COSs retard TLR2/4 dimerization and LPS recognition by TLR4, affecting downstream signaling cascades. In summary, this study provides a valuable insight into the potential anti-inflammatory mechanism of COSs and highlights the possible applications in human health promotion by modulating receptor-mediated signaling pathways.

We live in a world increasingly dominated by plastic, leading to the generation of microplastic particles that pose significant global health concerns. Microplastics can enter the body via ingestion, inhalation, and direct contact, accumulating in various tissues and potentially causing harm. Despite this, the specific cellular mechanisms and signaling pathways involved remain poorly understood. Macrophages are essential in absorbing, distributing, and eliminating microplastics, playing a key role in the body's defense mechanisms. Recent evidence highlights oxidative stress signaling as a key pathway in microplastic-induced macrophage dysfunction. The accumulation of microplastics generates reactive oxygen species (ROS), disrupting normal macrophage functions and exacerbating inflammation and organ damage. This review serves as the first comprehensive examination of the interplay between microplastics, macrophages, and oxidative stress. It discusses how oxidative stress mediates macrophage responses to microplastics and explores the interactions with gut microbiota. Additionally, it reviews the organ damage resulting from alterations in macrophage function mediated by microplastics and offers a novel perspective on the defense, assessment, and treatment of microplastic-induced harm from the viewpoint of macrophages.

This study aimed to investigate the inhibitory effects of soyasaponins extracted from soybean meal on thrombin, thereby providing scientific evidence for the application of soybean meal byproducts in functional foods and cardiovascular disease prevention. Using a combination of resin column chromatography and preparative liquid chromatography, six extracts were isolated and purified. Among these, four extracts (SE3, SE4, SE5, SE6) exhibited significant thrombin inhibitory activity. Enzyme activity assays revealed that SE6 showed the strongest inhibitory effect, with an IC50 of 1.36 mg mL-1. Component analysis indicated that SE3 contained a soyasaponins content as high as 91.2%, while SE4, SE5, and SE6 were mixtures of soyasaponins and isoflavones. Molecular docking analysis demonstrated that soyasaponins, such as Soyasapogenol E, had the highest binding affinity to thrombin. Moreover, the interactions of SE3, SE4, SE5, and SE6 with thrombin induced structural changes, reducing or eliminating the α-helical structures. These interactions were accompanied by fluorescence quenching effects, further elucidating the inhibition mechanism. The findings confirm that soyasaponins exhibit thrombin inhibitory activity. Additionally, a novel hypothesis was proposed, suggesting a potential synergistic effect between saponins and isoflavones. This synergy highlights the potential of soyasaponins and their complexes in the development of functional foods for cardiovascular health.

Perfluorooctanesulfonate (PFOS), an emerging contaminant with widespread concern, has been associated with the pathogenesis of atherosclerosis (AS). As a substitute for PFOS, sodium p-perfluorous nonenoxybenzenesulfonate (OBS) is extensively utilized in various applications and detected in human blood. However, its potential health risk in AS remain unclear. In this study, we investigated the comparative impacts of PFOS and OBS on endothelial dysfunction and atherogenesis. In the in vivo study, Apolipoprotein E knockout (ApoE-/-) mice were exposed to 0.4 or 4 mg/L PFOS/OBS for 12 weeks. We found that dyslipidemia developed more rapidly in the OBS-exposed mice than in the PFOS-exposed mice. PFOS exhibited a higher enrichment capacity in both blood and aortic tissues than OBS. Remarkably, OBS induced a more pronounced inflammatory response and caused a more significant disruption of the endothelial barrier in the aorta of ApoE-/- mice compared to PFOS. In vitro experiments showed that OBS, at the same exposure concentrations and durations as PFOS (0.1-20 μmol/L, 48 h), more effectively inhibited cell viability of human umbilical vein endothelial cells (HUVECs), caused higher levels of lactate dehydrogenase (LDH) release, and enhanced cell adhesion between HUVECs and monocytes. Both PFOS and OBS were found to activate the NF-κB signaling pathway and upregulate the expression of inflammatory factors. Notably, the use of OBS, but not PFOS, was shown to disrupt cell junctions and increase endothelial permeability by activating the MAPK/ERK signaling pathway. Our findings suggest that OBS may lead to endothelial dysfunction and have a greater impact on AS compared to PFOS, presenting significant health risks in cardiovascular diseases.

ANRIL, also referred to as CDKN2B-AS1, is a lncRNA gene implicated in the pathogenesis of multiple human diseases including atherosclerotic coronary artery disease, however, definitive in vivo evidence is lacking and the underlying molecular mechanism is largely unknown. In this study, we show that ANRIL overexpression causes atherosclerosis in vivo as transgenic mouse overexpression of full-length ANRIL (NR_003529) increases inflammation and aggravates atherosclerosis under ApoE-/- background (ApoE-/-ANRIL mice). Mechanistically, ANRIL reduces the expression of miR-181b-5p, which leads to increased TMEM106B expression. TMEM106B is significantly up-regulated in atherosclerotic lesions of both human CAD patients and ApoE-/-ANRIL mice. TMEM106B interacts and co-localizes with Na+-H+ exchanger NHE1, which results in mis-localization of NHE1 from cell membranes to lysosomal membranes, leading to increased lysosomal pH in macrophages. Large truncation and point mutation analyses define the critical amino acids for TMEM106B-NHE1 interaction and lysosomal pH regulation as F115 and F117 on TMEM106B and I537, C538, and G539 on NHE1. Topological analysis suggests that both N-terminus and C-terminus of NHE1 are located inside lysosomal lumen, and NHE1 is an important new proton efflux channel involved in raising lysosomal pH. A short TMEM106B peptide (YGRKKRRQRRR-L111A112V113F114F115L116F117) disrupting the TMEM106B-NHE1 interaction normalized lysosomal pH in macrophages with ANRIL overexpression. Our data demonstrate that ANRIL promotes atherosclerosis in vivo and identify the ANRIL/miR-181b-5p/TMEM106B-NHE1/lysosomal pH axis as the underlying molecular pathogenic mechanism for the chromosome 9p21.3 genetic locus for coronary artery disease.

Atherosclerosis is a slowly progressing inflammatory disease characterized with cholesterol disorder and intimal plaques. Asparagine endopeptidase (AEP) is an endolysosomal protease that is activated under acidic conditions and is elevated substantially in both plasma and plaques of patients with atherosclerosis. However, how AEP accelerates atherosclerosis development remains incompletely understood, especially from the view of cholesterol metabolism. This project aims to reveal the crucial substrate of AEP during atherosclerosis plaque formation and to lay the foundation for developing novel therapeutic agents for Atherosclerosis. Here, we show that AEP is augmented in the atherosclerosis plaques obtained from patients and proteolytically cuts apolipoprotein A1 (APOA1) and impairs cholesterol efflux and high-density lipoprotein (HDL) formation, facilitating atherosclerosis pathologies. AEP is activated in the liver and aorta of apolipoprotein E-null (APOE-null) mice, and deletion of AEP from APOE-/- mice attenuates atherosclerosis. APOA1, an essential lipoprotein in HDL for cholesterol efflux, is cleaved by AEP at N208 residue in the liver and atherosclerotic macrophages of APOE-/- mice. Blockade of APOA1 cleavage by AEP via N208A mutation or its specific inhibitor, #11a, substantially diminishes atherosclerosis in both APOE-/- and LDLR-/- mice. Hence, our findings support that AEP disrupts cholesterol metabolism and accelerates the development of atherosclerosis.

The lymphatic system functions by removing fluid, macromolecules, and immune cells to maintain tissue homeostasis. The structural organization of junctional protein complexes is vital to lymphatic function where initial lymphatics have permeable button junctions and collecting lymphatics have relatively impermeable zipper junctions. During inflammation, this junctional morphology appears to reverse, contributing to overall lymphatic malfunction. Little is known about the effects of immunomodulatory cytokines on lymphatic vessel formation and function during inflammation. The purpose of this study is to test the hypothesis that IL (interleukin)-19 promotes lymphangiogenesis and proper lymphatic function during inflammation.

We used cultured human dermal lymphatic endothelial cells to determine IL-19 expression and its effects on lymphangiogenesis assays. Immunocytochemistry and electric cell-substrate impedance sensing determined effects on junctional morphology as it relates to permeability in vitro. RNA sequencing determined the effects of IL-19 on gene expression. Il19-/-Ldlr-/- double knockout mice were used to determine IL-19 effects on lymphatic function and lymphatic vessel visualization in vivo.

Endogenous IL-19 expression is induced by exogenous IL-19 and VEGF (vascular endothelial growth factor) C stimulation. IL-19 is lymphangiogenic, increasing human dermal lymphatic endothelial cell migration, network formation, and proliferation. IL-19 induces expression of transcription factors and permeability-associated genes. IL-19 induces rapid VE-cadherin (vascular endothelial cadherin) phosphorylation, increases permeability of human dermal lymphatic endothelial cell monolayers, and mitigates oxidized low-density lipoprotein-associated decrease in human dermal lymphatic endothelial cell permeability. In vivo, Il19-/-Ldlr-/- double knockout mice on a high-fat diet have impaired lymphatic drainage, decreased lymphatic branch points, and increased percentage of zippered junctions compared with control mice.

Taken together, these data show that IL-19 has potent effects on lymphatic vessel formation and function in vitro and that IL-19 regulates lymphatic drainage in vivo. IL-19 may represent an immunomodulatory cytokine with therapeutic potential for improving impaired lymphatic function consequent to inflammation.

Stroke is the leading cause of mortality and morbidity worldwide, significantly impacting human welfare and overall health. Myeloperoxidase (MPO), a heme peroxidase secreted by neutrophils, plays a crucial role in the body's defense mechanisms, exhibiting pro-inflammatory and pro-oxidative properties. Additionally, MPO compromises the structural integrity and functional capacity of blood vessels, potentially leading to the formation and dislodgement of atherosclerotic plaques, vascular stenosis, thrombosis, and ultimately contributing to stroke occurrence. Following a stroke, a significant influx of neutrophils infiltrates the cerebral tissue, leading to an excessive release of MPO-derived oxidants and the subsequent promotion of various inflammatory mediators, thereby exacerbating cerebral tissue damage. Numerous studies have consistently demonstrated the pivotal role of MPO in the pathogenesis and progression of stroke, establishing it as a reliable prognostic indicator. Exploring the association between MPO and stroke enhances our understanding of the pathological mechanisms underlying stroke and aids in the development of therapeutic interventions. This review provides a comprehensive analysis of the molecular structure and cellular localization of MPO, elucidating its critical role in mediating vascular injury, the formation of Neutrophil Extracellular Traps (NETs), oxidative stress, neuroinflammation, disruption of the blood-brain barrier (BBB), and neuronal apoptosis during stroke pathogenesis. Additionally, we discuss recent advancements in MPO-targeted drugs and Traditional Chinese Medicine compounds as potential therapeutic strategies for stroke treatment.

Chronic inflammation is a hallmark for Metabolic Syndrome (MetS). It is also one of the most important risk factors for insulin resistance and metabolic disorders. Inflammasomes, which are intracellular multiprotein complexes within the innate immune system, regulate the production and maturation of pro-inflammatory cytokines including interleukin-1β (IL-1β) and IL-18 upon sensing pathogens or danger signals in the cytosol. A growing body of evidence indicates that inflammasomes play a pivotal role in the pathophysiology and progression of metabolic diseases, as deficiency in the key component of inflammasomes protects mice from high fat diet induced obesity and insulin resistance. Thus, in this review, we will summarize the role of inflammasomes in MetS and how to treat MetS by targeting inflammasomes. This may provide novel insights and therapeutic targets for treating metabolic disorders.

The publication focuses on the innovative applications of PROTAC (proteolysis-targeting chimera) technology in modern pharmacotherapy, with particular emphasis on cancer treatment. PROTACs represent an advanced therapeutic strategy that enables selective protein degradation, opening new possibilities in drug design. This technology shows potential in the treatment of cancers, viral infections (such as HIV and COVID-19), and chronic diseases including atherosclerosis, Alzheimer's disease, atopic dermatitis, and Huntington's disease. Promising results from clinical studies on the compound ARV-471 confirm the effectiveness of this approach. New types of PROTACs, like TF-PROTAC and PhosphoTAC, are designed to enhance the effectiveness, stability, and absorption of treatment drugs. The conclusions of the review highlight the broad therapeutic potential of PROTACs in various diseases and their relevance for the future of therapies, particularly in oncology.

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of plaque within the arteries. Despite advances in therapeutic strategies including anti-inflammatory, antioxidant, and lipid metabolism modulation treatments over the past two decades, the treatment of atherosclerosis remains challenging, as arterial damage is the result of interconnected pathological factors. Therefore, current monotherapies often fail to address the complex nature of this disease, leading to insufficient therapeutic outcomes. This review addressed this paucity of effective treatment options by comprehensively exploring the potential for combination therapies and advanced drug co-delivery systems for the treatment of atherosclerosis. We investigated the pathological features of and risk factors for atherosclerosis, underscoring the importance of drug combination therapies for the treatment of atherosclerotic diseases. We discuss herein mathematical models for quantifying the efficacy of the combination therapies and provide a systematic summary of drug combinations for the treatment of atherosclerosis. We also provide a detailed review of the latest advances in nanoparticle-based drug co-delivery systems for the treatment of atherosclerosis, focusing on the design of carriers with high biocompatibility and efficacy. By exploring the possibilities and challenges inherent to this approach, we aim to highlight cutting-edge technologies that can foster the development of innovative strategies, optimize drug co-administration, improve treatment outcomes, and reduce the burden of atherosclerosis-related morbidity and mortality on the healthcare system.

Cholesteryl ester hydrolase (CEH) is a critical enzyme in cholesterol ester hydrolysis, influencing cholesterol metabolism and efflux. This study demonstrates that CEH overexpression promotes free cholesterol efflux from macrophages, thereby reducing the lipid burden in existing atherosclerotic plaques. To enable targeted delivery, galactose-functionalized polyamidoamine (PAMAM) dendrimeric nanoparticles were utilized as nanocarriers for hepatic delivery of the CEH expression vector. The therapeutic potential of CEH plasmid-loaded dendrimeric nanoparticles was evaluated in Ldlr-/- mice. Results showed a significant reduction in total lesion area (21%) and aortic arch lesion area (23%) compared to baseline. Lesion component analysis revealed marked decreases in total cholesterol (36%), free cholesterol (35%), and cholesterol esters (44%). Collectively, these results support CEH overexpression as an effective strategy to enhance cholesterol efflux and mitigate lipid accumulation in atherosclerotic plaques. Moreover, galactose-functionalized PAMAM dendrimeric nanoparticles demonstrate strong potential as a targeted hepatic gene delivery system for therapeutic intervention in atherosclerosis.

Coronary artery atherosclerosis is a prevalent cardiovascular disease and a leading cause of major adverse cardiovascular events (MACE). Rotational atherectomy (RA) is an effective interventional technique for treating severe calcified stenosis. However, excessive forces, heat, and debris are prone to lead to serious surgical complications, such as slow flow/no-reflow and blood clots. To mitigate excessive force and heat generation during RA, a novel high-performance cutting tool was designed and fabricated for coronary artery calcified tissue removal. An RA simulation model was developed to simulate the procedure. The results showed that the forces, temperatures, and debris size remained within predefined safety thresholds. Using the 1.5 mm tool as an illustration, the peak cutting force was 1.062 N, and the peak temperature rise reached 1.170 °C. Debris distribution exhibited a normal pattern, with 90% of particles measuring below 14 μm. The experimental results closely matched the simulation values, showcasing errors under 10% and affirming the simulation model's precision. This research provides theoretical support for the study of mechanisms and contributes to optimizing the effectiveness of RA.

Atherosclerosis (AS) is a key mechanism in cardiovascular diseases and a major target for interventions. Jian-pi Qu-tan Hua-yu Decoction (JPQTHYD), a herbal formula, has been shown to alleviate AS.

This study aimed to evaluate the therapeutic effect of JPQTHYD on AS and explore its molecular mechanisms.

In vivo, we established a mouse model through a high-fat diet for 16 weeks combined with a 4-week exhaustive swimming experiment. The body weight and food intake of the mice were measured every 4 weeks. At the end of the 16 weeks, the moisture content of the mice's feces was measured, the morphology of the thoracic aorta and myocardium was observed using HE staining, and lipid deposition in the aorta and myocardium was assessed using Oil Red O staining. The ultrastructure of myocardial tissue was observed via transmission electron microscopy. Levels of TC, TG, and LDL-C were measured using an automatic biochemical analyzer. ELISA was used to detect the levels of ROS, IL-6, IL-10, TNF-α, hs-CRP, VCAM-1, and ICAM-1. In vitro, we induced HUVECs injury using 700 nM of Ang II. Cell viability was assessed using the CCK-8 assay, while ROS levels were measured by a ROS detection kit. NOX1 gene suppression was achieved using a NOX1 inhibitor. Protein expression levels of NOX1, ERK1/2, P-ERK1/2, VCAM-1, and ICAM-1 were measured by Western blot both in vivo and in vitro.

1. JPQTHYD improved fecal water content and exercise capacity in ApoE-/- mice. 2. JPQTHYD reduced TC, TG, LDL-C levels, decreased arterial intimal thickness, and inhibited atherosclerotic plaque formation. 3. JPQTHYD decreased proinflammatory factors and adhesion molecules by inhibiting the NOX1-ROS-ERK1/2 pathway. 4. In vitro, JPQTHYD suppressed endothelial inflammation by reducing NOX1-ROS-ERK1/2 signaling.

JPQTHYD reduced blood lipids, inhibited oxidative stress-induced inflammation, and alleviated AS in ApoE-/- mice, likely through the NOX1-ROS-ERK1/2 pathway. This study offers a novel investigation into the mechanisms and regulatory pathways through which traditional Chinese medicine contributes to the prevention and treatment of atherosclerosis.

Circadian rhythms in gut microbiota composition are crucial for metabolic function and disease progression, yet the diurnal oscillation patterns of gut microbiota in atherosclerotic cardiovascular disease (ASCVD) and their role in disease progression remain unknown. Here, we investigated gut bacterial dynamics in Apoe-/- mice over 24 hours and elucidated dynamic changes in fecal microbiota composition and function among C57BL/6 and Apoe-/- mice with standard chow diet or high-fat/high-cholesterol diet under ad libitum conditions. Compared with C57BL/6 mice, Apoe-/- mice exhibited significant differences in fecal microbial composition. Rhythmicity analysis revealed that the temporal dynamics of fecal microbiota composition and function in Apoe-/- mice differed significantly from those in C57BL/6 mice, particularly in B. coccoides-dominated oscillatory modules. Functional annotation showed that rhythmic B. coccoides strains inhibited ASCVD progression by enhancing intestinal and endothelial barrier functions. These findings demonstrate that diurnal oscillations in gut microbiota are closely associated with ASCVD progression and provide new insights for microbiota-targeted precision therapies.

This study investigates the knowledge, attitudes, and practices (KAP) regarding atherosclerosis ultrasound screening among adults in the general population of Shanghai. A cross-sectional study was conducted from April 5 to May 30, 2024, at the Department of Ultrasound Medicine, Shanghai Eighth People's Hospital, involving the general public. An investigator-designed questionnaire collected demographic information and KAP scores. Path analysis was performed to assess the relationships between overall KAP scores, with subgroup analysis for participants with atherosclerotic cardiovascular disease (CVD). A total of 617 valid questionnaires were analyzed, revealing a high reliability coefficient of 0.949. Mean KAP scores were as follows: knowledge 9.73 ± 5.80 (/24, 40.54%), attitude 56.38 ± 10.94 (/65, 86.74%), and practice 21.66 ± 5.54 (/35, 61.89%), indicating poor knowledge but positive attitudes and proactive practices. Knowledge significantly influenced both attitude (β = 0.354, P = 0.028) and practice (β = 0.357, P = 0.021). In participants with CVD, mean scores were 11.14 ± 4.10 for knowledge, 59.69 ± 11.94 for attitude, and 23.17 ± 5.32 for practice. In the general Shanghai population, knowledge about atherosclerosis ultrasound screening is poor, yet attitudes are positive, and practices are proactive. Targeted educational interventions are necessary to enhance knowledge and attitudes, thus improving screening practices.

Atherosclerosis (AS) is a cardiovascular disease that is caused by a variety of factors, including hypertension, diabetes, hyperlipidaemia and smoking. Circular RNAs (circRNAs) have been reported to participate in the progression of AS. Here, we investigated the mechanism by which circ-proteasome 20 S subunit beta 1 (PSMB1) participates in AS.

HAECs were stimulated with oxidized low-density lipoprotein (ox-LDL) to establish a model of AS in vitro. Cell viability was investigated with MTT assays. Western blotting and qRT‒PCR were used to measure relative protein and mRNA expression. Cell pyroptosis was analysed by flow cytometry. Lactate dehydrogenase (LDH) levels were measured with a commercial kit.

We found that circ-PSMB1 and apoptosis-associated speck-like protein containing a CARD (ASC) were overexpressed and miR-624-3p was expressed at low levels in HAECs treated with ox-LDL. Circ-PSMB1 silencing enhanced cell viability and decreased pyroptosis, as shown by the downregulation of IL-1β and IL-18 mRNA expression as well as NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and GasderminD-N (GSDMD-N) protein expression. In addition, the miR-624-3p inhibitor neutralized the effects of si-circ-PSMB1, and ASC overexpression neutralized the effects of the miR-624-3p mimic in ox-LDL-treated HAECs.

This research demonstrated that circ-PSMB1 might participate in AS development through regulating the pyroptosis of HAECs via the miR-624-3p/ASC axis.