Biomarkers Of Atherosclerosis Research Articles

A U-shaped relationship between the atherogenic index of plasma and repeated target vessel revascularization in patients undergoing percutaneous coronary intervention: a retrospective study

BackgroundAtherogenic index of plasma (AIP) has been recognized as a novel and practical marker for the assessment of cardiometabolic risk, but the relevance of AIP as a prognostic biomarker in coronary artery disease (CAD) remains debated. This study investigated the association between AIP and major adverse cardiac and cerebrovascular events (MACCEs) in CAD patients receiving percutaneous coronary intervention (PCI) with drug-eluting stents (DES).MethodsA total of 2,250 patients undergoing PCI with DES were included in this retrospective cohort study. The primary endpoint was MACCEs, encompassing acute myocardial infarction, repeat target vessel revascularization (TVR), stroke, and all-cause mortality. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were applied to explore the dose–response associations. And subgroup analysis was conducted to evaluate potential relationship between AIP and MACCEs across different subgroups.ResultsDuring a medium follow-up of 29.8 (25.6–34.0) months, 106 (4.7%) patients experienced TVR. After adjusting for confounders, AIP (per 1 SD increase) was positively associated with TVR (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.01–1.58, P = 0.042). In females, there was a significant association (OR = 2.33, 95% CI = 1.40–3.98, P = 0.002), but no significant association was observed in males. There was an interaction between AIP and gender (P = 0.017). Restricted cubic spline analysis depicted a U-shaped relationship between AIP and TVR (Pnonlinear = 0.016), with an elevated risk evident from an AIP of 0.20.ConclusionAIP showed a U-shaped relationship with TVR in PCI patients with DES, particularly pronounced among females. We suggested that the AIP should be used as a plasma marker of key interest for preventing TVR after DES implantation in patients with CAD.

Distinct Metabolites in Atherosclerosis Based on Metabolomics: A Systematic Review and Meta-analysis Primarily in Chinese Population

AimsAtherosclerosis is a life-threatening disease that develops when a plaque builds up inside an artery and progresses silently. Identifying the early pathological changes and the biomarkers of atherosclerosis deserves attention. We aimed to systematically study and integrate the various metabolites of atherosclerosis in the level of disease to provide more evidences to support early prevention and treatment of atherosclerosis. Data synthesisThe protocol was registered with PROPSERO (CRD42023441845). We searched 14985 records via EMBASE, PubMed, Web of Science, WanFang data, VIP data, and CNKI databases. The collected metabolites were for qualitative and quantitative meta-analysis. The I2 statistic estimated heterogeneity, with over 50% considered to adopt the random-effects model. A total of 49 articles were included in the meta-analysis. We finally integrated 83 and 16 metabolites presented more than two times in inclusion studies, respectively in blood (plasma and serum) and urine. Among them, the level of citric acid (SMD=-10.35 [95%CI -15.03, -5.67], p<0.001), lactic acid (SMD= 6.32 [95%CI 0.12, 12.52], p<0.001) and TMAO (SMD= 1.40 [95%CI 0.27, 2.53], p<0.001) had significant differences between atherosclerosis and controls. And we observed blood stasis syndrome of atherosclerosis patients present arterial ischemia and energy disorder obviously. ConclusionsThe study provides an in-depth understanding of the roles of metabolites on atherosclerosis progression and prediction primarily in Chinese population, which contributing to development of prevention and therapeutic potential in the future.

Anti-inflammatory Activity of Clitoria ternatea L. and Hibiscus sabdariffa L. Extract Combination in Reducing VCAM-1 Levels in Atherosclerosis

Atherosclerosis occurs when plaque accumulates and hardens within the arterial walls, leading to blood vessel blockages and increasing the risk of coronary heart disease (CHD). The extracts of butterfly pea (Clitoria ternatea L.) and roselle (Hibiscus sabdariffa L.) contain flavonoids that possess strong antioxidant and anti-inflammatory properties. This study aims to assess the effects of the combined extract of butterfly pea and roselle (EKTR) on atherosclerosis biomarkers such as Vascular Cell Adhesion Molecules-1 (VCAM-1), Intercellular Adhesion Molecule-1 (ICAM-1), and Interleukin-6 (IL-6). The research employed a True Experimental Laboratory approach using a Post-Test Control Group Design. The subjects were 36 female Wistar rats (Rattus norvegicus L.), randomly divided into six groups through a Completely Randomized Design (CRD). Data were collected on the levels of VCAM-1, ICAM-1, and IL-6 in the serum of obese white rats, measured using an ELISA photometer. Data analysis was conducted using SPSS version 18, with statistical evaluation performed via one-way ANOVA and Tukey's post hoc test. The results showed that increasing doses of EKTR led to significant reductions in atherosclerosis biomarkers such as VCAM-1, ICAM-1, and IL-6 compared to the positive control and other groups. At a dose of 500 mg/kg BW, group F3 recorded IL-6 levels of 30.49 ± 1.60 ng/mL, VCAM-1 level of 29.42 ± 2.58 ng/mL, and ICAM-1 levels of 28.42 ± 1.72 ng/mL. In conclusion, butterfly pea and roselle, rich in flavonoids with potent antioxidant and anti-inflammatory properties, are effective as traditional remedies for reducing atherosclerosis biomarkers and for preventing and treating coronary heart disease (CHD) at an optimal dose of 500 mg/kg BW.

Unraveling the proteomic signatures of coronary artery disease and hypercholesterolemia.

Atherosclerosis, a leading cause of coronary artery disease (CAD), is heavily influenced by hypercholesterolemia (HC). Proteomics research has shown promise in identifying biological markers for CAD diagnosis and prognosis. This cross-sectional study aimed to identify novel biomarkers for detecting HC and CAD. Through the analysis of proteome data from healthy controls (n=45) and patients diagnosed with HC (n=51) or CAD (n=32), distinct protein patterns associated with each condition were identified. Significant alterations in protein levels were identified with a false discovery rate (FDR)-corrected q-value of <0.05. Subsequent receiver operating characteristic (ROC) analysis, with an area under the curve (AUC) greater than 0.75, was conducted. CAD patients exhibited significantly increased levels of the cholesterol-metabolizing protein PCSK9 and varied levels of the angiogenesis-related protein SDF-1 compared to controls. In pairwise comparisons among the study groups, 65 proteins showed significant differential expression. Notably, 14 of these proteins had significant correlations with blood cholesterol levels. Additionally, 22 of the identified proteins were associated with CAD or HC pathways, with nine proteins being common to both conditions (Apo E, Apo E3, MMP-3, PCSK9, SDF-1, Apo B, PAFAH, HSP 60, and TAK1-TAB1). Nevertheless, this is an exploratory study, and validation studies are needed to confirm these potential protein biomarkers for CAD in the context of HC.

Assessment of Paraoxonase 1 and Arylesterase Activities and Lipid Profile in Bodybuilders: A Comparative Study of Physical Activity and Anthropometry on Atherosclerosis.

Background and Objectives: Atherosclerosis, driven by dyslipidaemia and oxidative stress, is a leading cause of cardiovascular morbidity and mortality. This study evaluates the effects of vigorous-intensity bodybuilding exercise (VIBBE) on atherosclerosis biomarkers-including paraoxonase-1 (PON1) and arylesterase (ARE) activities-and lipid profiles in male bodybuilders who do not use anabolic-androgenic steroids. Comparisons were made with individuals engaged in moderate-intensity aerobic exercise (MIAE), as well as overweight/obese sedentary (OOS) and normal-weight sedentary (NWS) individuals. Materials and Methods: A cross-sectional study was conducted involving 122 healthy male participants aged 18-45 years, divided into four groups: VIBBE (n = 31), OOS (n = 30), MIAE (n = 32), and NWS (n = 29). Anthropometric assessments were performed, and fasting blood samples were collected for biochemical analyses, including lipid profiles and PON1 and ARE activities. Statistical analyses compared the groups and evaluated correlations between adiposity measures and atherosclerosis biomarkers. Results: The VIBBE group exhibited significantly lower levels of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and logarithm of the TG to high-density lipoprotein cholesterol (HDL-C) ratio [log(TG/HDL-C)] compared to the OOS group (p < 0.05 for all), indicating improved lipid profiles. However, these improvements were not significant when compared to the NWS group (p > 0.05), suggesting that VIBBE may not provide additional lipid profile benefits beyond those associated with normal weight status. PON1 and ARE activities were significantly lower in the VIBBE group compared to the MIAE group (p < 0.05 for both), suggesting that VIBBE may not effectively enhance antioxidant defences. Correlation analyses revealed significant inverse relationships between PON1 and ARE activities and adiposity measures, including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body fat percentage (BFP), fat mass index (FMI), and obesity degree (OD) (p < 0.05 for all). Positive correlations were observed between oxLDL and log(TG/HDL-C) and adiposity measures (p < 0.05 for all). Conclusions: Vigorous-intensity bodybuilding exercise improves certain lipid parameters compared to sedentary obese individuals but does not significantly enhance antioxidant enzyme activities or further improve lipid profiles beyond those observed in normal-weight sedentary men. Conversely, moderate-intensity aerobic exercise significantly enhances PON1 and ARE activities and improves lipid profiles, offering superior cardiovascular benefits. These findings underscore the importance of incorporating moderate-intensity aerobic exercise into physical activity guidelines to optimize cardiovascular health by balancing improvements in lipid metabolism with enhanced antioxidant defences.

Inflammatory and Lipid Biomarkers in Early Atherosclerosis: A Comprehensive Analysis

Introduction: Atherosclerosis is a leading cause of cardiovascular disease, characterized by lipid accumulation and chronic inflammation within arterial walls. Early detection in young adults is crucial for preventing adverse cardiovascular events. This study investigates the associations between inflammatory indices, lipid biomarkers, and the presence of atherosclerosis in patients aged 18 to 55 years. Methods: A cross-sectional study was conducted involving 89 participants divided into two groups: 62 patients with documented atherosclerosis (main group) and 27 healthy controls without significant atherosclerosis. Comprehensive data—including demographic information, medication use, imaging results, laboratory parameters, and calculated inflammatory indices (SIRI, SII, AISI, NLR, PLR, MLR)—were collected. Statistical analyses included correlation assessments, group comparisons using the Mann–Whitney U test, logistic regression modeling, feature importance analysis with Random Forest and Gradient Boosting classifiers, receiver operating characteristic (ROC) curves, and K-means clustering. Results: Significant differences were observed between the main and control groups. Patients with atherosclerosis exhibited elevated inflammatory indices (SIRI, NLR, MLR, SII) and lipid profile abnormalities (higher TC and LDL-C, lower HDL-C). Lp(a) and ANGPTL3 levels were significantly higher in the main group (p &lt; 0.001 and p &lt; 0.01, respectively). Logistic regression identified SIRI and ANGPTL3 as significant predictors of atherosclerosis, with the model demonstrating high accuracy (77%) and sensitivity (93%). Feature importance analysis confirmed the significance of SIRI and ANGPTL3, alongside traditional lipid biomarkers, in predicting disease presence. ROC analysis showed excellent model performance (AUC &gt; 0.80). Clustering analysis revealed two distinct patient subgroups characterized by predominant inflammatory profiles or lipid metabolism disturbances. Conclusions: Systemic inflammation and lipid abnormalities play significant roles in early atherosclerosis among young adults. Elevated SIRI and ANGPTL3 levels are potent predictors of disease presence. The integration of inflammatory indices and lipid biomarkers into predictive models enhances risk stratification and supports personalized medicine approaches.

Identification of novel biomarkers for atherosclerosis using single-cell RNA sequencing and machine learning.

Atherosclerosis (AS) is a predominant etiological factor in numerous cardiovascular diseases, with its associated complications such as myocardial infarction and stroke serving as major contributors to worldwide mortality rates. Here, we devised dependable AS-related biomarkers through the utilization of single-cell RNA sequencing, weighted co-expression network (WGCNA), and differential expression analysis. Furthermore, we employed various machine learning techniques (LASSO and SVM-RFE) to enhance the identification of AS biomarkers, subsequently validating them using the GEO dataset. Following this, CIBERSORT was employed to investigate the correlation between biomarkers and infiltrating immune cells. Consequently, 256 differentially expressed genes (DEGs) were selected in samples of AS and normal. GO and KEGG analyses indicated that these DEGs may be related to the negative regulation of leukocyte-mediated immunity, leukocyte cell-cell adhesion, and immune system processes. Notably, C1QC and COL1A1 were pinpointed as potential diagnostic markers for AS, a finding that was further validated in the GSE21545 dataset. Moreover, the area under the curve (AUC) values for these markers exceeded 0.8, underscoring their diagnostic utility. Analysis of immune cell infiltration revealed that the expression of C1QC was correlated with M0 macrophages, gamma delta T cells, activated mast cells and memory B cells. Similarly, COL1A1 expression was linked to M0 macrophages, memory B cells, activated mast cells, gamma delta T cells, and CD4 native T cells. Finally, these results were validated using mice and human samples through immunofluorescence, immunohistochemistry, and ELISA analysis. Overall, C1QC and COL1A1 would be potential biomarkers for AS diagnosis, and that would provides novel perspectives on the diagnosis and treatment of AS.

Old, the new, more or less and the conundrum for biomarkers in cardiovascular diseases?

Biomarkers are critical for diagnostic, monitoring and management of cardiovascular diseases. Opportunities to improve how biomarkers are used are important. This editorial on biomarkers in coronary artery disease provides commentary on the study as well as broad benchmarks on what make ideal biomarkers. Biomarker discovery is difficult and opportunities to expand and improve their use should be encouraged.

Colchicine effect on biomarkers of cardiac remodelling and atherosclerosis in ST-elevation myocardial infarction: A randomized controlled trial.

Owing to its underlying inflammatory nature, atherosclerotic cardiovascular disease remains the leading global cause of mortality, particularly post-ST-elevation myocardial infarction (STEMI), a condition with significant risk for further cardiovascular events and mortality. This study aimed to investigate colchicine's effect on inflammation, cardiac remodelling and atherosclerotic risk in STEMI patients. We conducted a randomized controlled study on 88 STEMI patients undergoing percutaneous coronary intervention. Eligible patients were randomly assigned to 1 of 2 groups. The control group received the guideline-directed medical therapy for STEMI, and the test group received guideline-directed medical therapy and 0.5mg colchicine twice daily for 3months. The soluble suppressor of tumorigenicity (sST2), interleukin-1β, lipid profile parameters, triglyceride (TG)/high-density lipoprotein (HDL-C) ratio levels and left ventricular ejection fraction were evaluated for patients at baseline and the end of the 3months. No significant effects were reported for colchicine on sST2, interleukin-1β levels or left ventricular ejection fraction. Colchicine significantly lowered TG levels vs. controls, 134 (46-353) vs. 176 (72-825) respectively, P= .02, as well as TG/HDL-C ratio levels, 4.16 (2.75-5.24) vs. 5.11 (3.51-8.33),` respectively, P= .024. sST2 levels of the studied cohort were positively correlated with their TG/HDL-C ratio levels (R= .459, P< .001) at the end of follow-up. Our study highlights a promising impact of colchicine on atherosclerosis and cardiac remodelling factors in STEMI patients. Colchicine significantly reduced TG levels and TG/HDL-C ratio and was safe and well tolerated. Larger long-term studies powered to assess clinical outcomes of remodelling are necessary to confirm its beneficial effects in STEMI. NCT06054100.

LncRNA MBNL1-AS1 functions as an alternative atherosclerosis biomarker in elderly hypertensive patients and regulates vascular smooth muscle cell function.

The clinical role of long non-coding RNA (MBNL1-AS1) in diagnosing atherosclerosis (AS) risks of hypertensive patients and the effects of MBNL1-AS1 on vascular smooth muscle cells (VSMCs) triggered by angiotensin II (Ang II) were investigated. The hypertensive patients were recruited to assess MBNL1-AS1 expression. The ROC curve and Spearman analysis was performed for the significance of MBNL1-AS1. Human VSMCs were treated with Ang II (10-5 mol/L) to establish a hypertensive cell model. MTT and Transwell chamber were used in proliferative and migratory detection of cell models. Targets of MBNL1-AS1 were verified by luciferase activity. Functional enrichment of shared targets of miR-424-5p was researched by GO and KEGG analysis. An increase of MBNL1-AS1 was observed in patients with increased carotid intima-media thickness (cIMT). MBNL1-AS1 could predict the risk of AS and related to cIMT levels. The knockdown of MBNL1-AS1 mitigated the influence of Ang II on cellular proliferation and migration by inhibiting miR-424-5p. Enrichment analysis corroborated that targets of miR-424-5p were mainly involved in serine/threonine kinase activity, MAPK signaling pathway, and PI3K-Akt signaling pathway. MBNL1-AS1/miR-424-5p axis was connected with the progression of AS induced by hypertension.

Evaluation of Novel Biomarker of Early Atherosclerosis in Patients With Chronic Kidney Disease in Wasit Governorate

The aim of the study was to evaluate some Biomarkers in patients with athreoscelerosis in Wasit Province. Atherosclerosis is a chronic arterial disease and a major cause of vascular death. Fatty streaks in arterial walls gradually develop into atheroma and characteristic plaques. The acute rupture of these atheromatous plaques causes local thrombosis, leading to partial or total occlusion of the affected artery. The clinical consequences of these plaques depend on their site and the degree and speed of vessel occlusion . Its major clinical manifestations include ischemic heart disease (IHD), ischemic stroke, and peripheral arterial disease. The study took place in the a hemodialysis unit Al-Zahraa Teaching Hospital in Wasit Governorate during the period from November 2023 to April 2024. This study aimed to examine risk factors (age, gender, high blood pressure, smoking, left ventricular hypertrophy, diabetes mellitus, dyslipidemia, physical inactivity) for atherosclerosis in the general population and patients with chronic kidney disease. Also studying the effect of some novel biomarkers (Homocysteine, Fibrinogen, myeloperoxidase, lipoprotein-associated phospholipase A2, pentraxin 3). The study include (90) samples: (60) patients suffering from early atherosclerosis and chronic kidney disease (dialysis stage) and 30 samples of healthy people (control group), their ages ranged from (40 to 70 years). The samples were divided into two age groups, where the first group had an average age of 40-55 years and the second group was 56-70 years old , the categories were divided equally into males and females Samples were collected based on the incidence of kidney disease first, and then the main risk factors of early atherosclerosis were relied upon, which are (smoking, age, sex, dyslipidemia, hypertension, diabetes, left ventricle valve, physical inactivity). The results of our study regarding diagnostic markers of atherosclerosis showed a significant increase in biomarkers (MPO, PTX3, HCy, FG and LpPLA2)of infected people at p ≥ 0.5. In patients with atherosclerosis the level of new biomarkers showed a significant increase in serum of infected people compared to healthy people at p&lt;0.5. This is an important indication of the importance of these biomarkers in detecting the disease.

Association of hsCRP and Serum Kalirin Levels with the Development and Severity of Premature Coronary Artery Disease in Iraqi Patients

Background: Coronary artery disease (CAD) is a major contributor to morbidity and mortality worldwide. Early-onset CAD, also known as PCAD, is a severe form of CAD associated with high mortality and a poor prognosis. Early diagnosis is crucial to reducing complications. While hsCRP is an established biomarker for CAD, kalirin is a potential novel biomarker due to its role in promoting smooth muscle proliferation and endothelial dysfunction. Objective: To evaluate the relationship between serum kalirin and hsCRP levels with the presence and severity of PCAD and to compare the diagnostic value of both biomarkers. Method: The study recruited 92 participants into two groups: the PCAD group (46) included patients with confirmed CAD by angiographic findings and the second group was the non-CAD group (46) with negative findings by coronary angiography. The levels of serum kalirin and hsCRP were measured for both groups using enzyme-linked immunosorbent assay (ELISA) kits. Results: Serum levels of kalirin and hsCRP were strongly associated with the presence of PCAD (p&lt;0.001), and both biomarkers were associated with disease severity (p=0.002, &lt;0.001, respectively). ROC analysis showed that hsCRP possesses a slight advantage (AUC=0.796) over kalirin (ROC=0.717) as a diagnostic marker for PCAD. Conclusions: Serum kalirin and hsCRP levels are associated with PCAD and with the severity of the disease, both markers possess moderate diagnostic capabilities for PCAD with a slight advantage for hsCRP.

Comparison of the oral microbiota of patients with atherosclerosis and healthy controls by denaturing gradient gel electrophoresis.

Oral infections can activate local and systemic inflammation. The inflammatory response plays a main role in atherosclerosis. several studies have reported a relation between oral pathogen infection and Atherosclerosis. Recently it was indicated that some oral microbiome has a significant role in triggering atherosclerosis. Denaturing Gradient Gel Electrophoresis (DGGE) is an acceptable assay for identification of uncultivable bacteria. Therefore, we compared the bacterial population diversity in the oral microbiota between atherosclerosis patients and healthy people. Oral microbiota profiling was performed for 139 individuals including 89 patients with CAD and 50 healthy individuals. After DNA extracted from saliva, PCR products were examined and evaluated using DGGE assay. We found that significant relationship between the increased risk of atherosclerosis and the presence of Actinomyces oris, Enterococcus faecalis, Bacterium strain sulresv, Bacterium Culaenoe, NC4, NC7, and NC5 in atherosclerosis patients and healthy individuals. There was also a significant relationship between reducing the risk of atherosclerosis in the presence of NC3 and Entreococcus munotii in atherosclerosis patients and healthy individuals. In conclusion, presence of some oral microbiota increases the risk of atherosclerosis and the presence of some oral microbiota reduces the risk, so the oral microbiota should be further examined to determine its potential as a biomarker for atherosclerosis.

Circulating miRNAs as Biomarkers of Subclinical Atherosclerosis Associated with Severe Obesity before and after Bariatric Surgery.

Severe obesity results in high cardiovascular risk (CVR), increasing morbidity, and mortality. New and improved methods are needed to detect cardiovascular diseases rapidly in severe obesity. microRNAs (miRNAs) has shown promise as diagnostic tools. This study aimed to identify plasma miRNAs useful as biomarkers of CVR in people with severe obesity. The study included 66 people with severe obesity classified in groups with atheroma (n = 32) and free of plaques (n = 34). Plasma samples were collected 1 month before bariatric surgery and at 6 and 12 months of follow-up. Participants were screened for the levels of 188 miRNAs, and 24 promising candidates were individually validated by quantitative polymerase chain reaction. After validation, 5 of the 24 miRNAs showed significant differences over time in both groups: miR-375 increased after bariatric surgery, whereas miR-144-5p, miR-20a-3p, miR-145-5p, and miR-21-3p exhibited decreased expression after bariatric surgery. The expression of 3 of the 24 miRNAs also differed between patients with and without atheroma: subjects with plaque had lower miR-126 but higher miR-21-3p and miR-133a-3p. Only miR-133a-3p exhibited exceptional discriminatory ability between subjects with and without plaque (area under the curve, 0.90; 95% confidence interval, 0.81-0.99). A specific signature of c-miRNA comprising miR-375, miR-144-5p, miR-20a-3p, miR-145-5p, and miR-21-3p may facilitate CVR monitoring after bariatric surgery. Furthermore, miR-21-3p, miR-126-3p, and miR-133a-3p show potential as specific biomarkers for subclinical atherosclerosis, with miR-133a-3p potentially able to diagnose subclinical atherosclerosis early in severe obesity.

Postmortem-Derived Exosomal MicroRNA 486-5p as Potential Biomarkers for Ischemic Heart Disease Diagnosis.

Exosomes are nanovesicles 30-150 nm in diameter released extracellularly. Those isolated from human body fluids reflect the characteristics of their cells or tissues of origin. Exosomes carry extensive biological information from their parent cells and have significant potential as biomarkers for disease diagnosis and prognosis. However, there are limited studies utilizing exosomes in postmortem diagnostics. In this study, we extended our initial research which identified the presence and established detection methodologies for exosomes in postmortem fluids. We analyzed exosomal miRNA extracted from plasma and pericardial fluid samples of a control group (n = 13) and subjects with acute myocardial infarction (AMI; n = 24). We employed next-generation sequencing (NGS) to investigate whether this miRNA could serve as biomarkers for coronary atherosclerosis leading to acute myocardial infarction. Our analysis revealed 29 miRNAs that were differentially expressed in the AMI group compared to the control group. Among these, five miRNAs exhibited more than a twofold increase in expression across all samples from the AMI group. Specifically, miR-486-5p levels were significantly elevated in patients with high-grade (type VI or above) atherosclerotic plaques, as per the American Heart Association criteria, highlighting its potential as a predictive biomarker for coronary atherosclerosis progression. Our results indicate that postmortem-derived exosomal microRNAs can serve as potential biomarkers for various human diseases, including cardiovascular disorders. This finding has profound implications for forensic diagnostics, a field critically lacking diagnostic markers.

IL-6R (trans-signaling) is a key regulator of reverse cholesterol transport in lipid-laden macrophages

Atherosclerosis is a cardiovascular disease caused by cholesterol-laden arterial plaques. This study evaluated the correlation between interleukin-6 (IL-6), its receptors (IL6R/CD126), and glycoprotein 130 (gp130) alongside atherosclerosis biomarkers in a cohort of 142 subjects, equally divided between lean and obese individuals. Subsequent analyses used THP-1-derived macrophages to assess the biochemical impact of inhibiting IL-6 receptors. IL-6 secretion increased with atherosclerosis in obese subjects, while IL6R/CD126 and gp130 on monocytes decreased. Pharmacological gp130 inhibition altered lipid metabolism, increasing LDLR gene expression and cholesterol synthesis via SREBF2 and mevalonate kinase, along with HMG-CoA reductase at protein levels. gp130-deficient cells produced more cholesterol and had lower ABCA1 levels, suggesting hindered cholesterol efflux. Filipin III staining confirmed cholesterol retention in gp130-inhibited cells. Ex-vivo investigation on lean PBMCs further defined the impact of gp130 inhibition on the reduction of cholesterol efflux. Our results indicates gp130 is crucial for macrophage reverse cholesterol transport and may be a target for atherosclerosis treatments.

LRG1 promotes atherosclerosis by inducing macrophage M1-like polarization

Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by the accumulation of cholesterol-rich lipoproteins in macrophages. How macrophages commit to proinflammatory polarization under atherosclerosis conditions is not clear. Report here that the level of a circulating protein, leucine-rich alpha-2 glycoprotein 1 (LRG1), is elevated in the atherosclerotic tissue and serum samples from patients with coronary artery disease (CAD). LRG1 stimulated macrophages to proinflammatory M1-like polarization through the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways. The LRG1 knockout mice showed significantly delayed atherogenesis progression and reduced levels of macrophage-related proinflammatory cytokines in a high-fat diet-induced Apoe-/- mouse atherosclerosis model. An anti-LRG1 neutralizing antibody also effectively blocked LRG1-induced macrophage M1-like polarization in vitro and conferred therapeutic benefits to animals with ApoE deficiency-induced atherosclerosis. LRG1 may therefore serve as an additional biomarker for CAD and targeting LRG1 could offer a potential therapeutic strategy for CAD patients by mitigating the proinflammatory response of macrophages.

MiRNAs as potential biomarkers for subclinical atherosclerosis in Sjögren’s disease

BackgroundMicroRNAs (miRNAs) can regulate gene expression, controlling numerous cellular processes. Dysregulation of miRNA function is linked to various diseases, making them attractive diagnostic and therapeutic targets. Examples include hsa-miR-92a-3p, hsa-miR-126-3p,...

Circulating monocyte phenotype: A novel biomarker of atherosclerosis

Circulating monocyte phenotype: A novel biomarker of atherosclerosis

Characterization of the human macrophage spectrum: A novel approach to identify novel drug targets and biomarkers in atherosclerosis

Characterization of the human macrophage spectrum: A novel approach to identify novel drug targets and biomarkers in atherosclerosis