Atherosclerosis (AS) is a complex pathology process involving intricate interactions among various cells and biological processes. Vascular smooth muscle cells (VSMCs) are the predominant cell type in normal arteries, and under atherosclerotic stimuli, VSMCs respond to altered blood flow and microenvironment changes by downregulating contractile markers and switching their phenotype. This review overviews the diverse phenotypes of VSMCs, including the canonical contractile VSMCs, synthetic VSMCs, and phenotypes resembling macrophages, foam cells, myofibroblasts, osteoblasts/chondrocytes, and mesenchymal stem cells. We summarize their presumed protective and pro-atherosclerotic roles in AS development. Additionally, we underscore the molecular mechanisms and regulatory pathways governing VSMC phenotypic switching, encompassing transcriptional regulation, biochemical factors, plaque microenvironment, epigenetics, miRNAs, and the cytoskeleton, emphasizing their significance in AS development. Finally, we outline probable future research directions targeting VSMCs, offering insights into potential therapeutic strategies for AS management.

Lipid-lowering therapy is an important tool for the treatment of lipid metabolic diseases, which are increasing in prevalence. However, the failure of conventional lipid-lowering drugs to achieve the desired efficacy in some patients, and the side-effects of these drug regimens, highlight the urgent need for novel lipid-lowering drugs. The liver and intestine are important in the production and removal of endogenous and exogenous lipids, respectively, and have an important impact on circulating lipid levels. Elevated circulating lipids predisposes an individual to lipid deposition in the vascular wall, affecting vascular function. Berberine (BBR) modulates liver lipid production and clearance by regulating cellular targets such as cluster of differentiation 36 (CD36), acetyl-CoA carboxylase (ACC), microsomal triglyceride transfer protein (MTTP), scavenger receptor class B type 1 (SR-BI), low-density lipoprotein receptor (LDLR), and ATP-binding cassette transporter A1 (ABCA1). It influences intestinal lipid synthesis and metabolism by modulating gut microbiota composition and metabolism. Finally, BBR maintains vascular function by targeting proteins such as endothelial nitric oxide synthase (eNOS) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). This paper elucidates and summarizes the pharmacological mechanisms of berberine in lipid metabolic diseases from a multi-organ (liver, intestine, and vascular system) and multi-target perspective.

Circulating miRNAs can function as biomarkers for diagnosis, treatment, and prevention of diseases. However, it is unclear whether miRNAs can be used as biomarkers for acute coronary syndrome (ACS). To this end, we applied gene chip technology to analyze miRNA expression in patients with stable angina (SA), non-ST elevation ACS (NSTE-ACS), and ST-segment elevation myocardial infarction (STEMI). We enrolled patients with chest pain who underwent diagnostic coronary angiography, including five patients each with SA, NSTE-ACS, or STEMI, and five controls without coronary artery disease (CAD) but with three or more risk factors. After microarray analysis, differential miRNA expression was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Compared with those in patients with STEMI, differentially expressed microRNAs in controls and patients with SA or NSTE-ACS were involved in inflammation, protein phosphorylation, and cell adhesion. Pathway analysis showed that differentially expressed miRNAs were related to the mitogen-activated protein kinase signaling, calcium ion pathways, and cell adhesion pathways. Compared with their expression levels in patients with STEMI, miR-941, miR-363-3p, and miR-182-5p were significantly up-regulated (fold-change: 2.0 or more, P < 0.05) in controls and patients with SA or NSTE-ACS. Further, qRT-PCR showed that plasma miR-941 level was elevated in patients with NSTE-ACS or STEMI as compared with that in patients without CAD (fold-change: 1.65 and 2.28, respectively; P < 0.05). Additionally, miR-941 expression was significantly elevated in the STEMI group compared with that in the SA (P < 0.01) and NSTE-ACS groups (P < 0.05). Similarly, miR-941 expression was higher in patients with ACS (NSTE-ACS or STEMI) than in patients without ACS (without CAD or with SA; P < 0.01). There were no significant differences in miR-182-5p and miR-363-3p expression. The areas under the receiver operating characteristic curves were 0.896, 0.808, and 0.781 for patients in the control, SA, and NSTE-ACS groups, respectively, compared with that for patients with STEMI; that for the ACS group compared with the non-ACS group was 0.734. miR-941 expression was relatively higher in patients with ACS and STEMI. Thus, miR-941 may be a potential biomarker of ACS or STEMI.

Background: Selenium is a trace element that has been reported to be effective in regulating glucose and lipid metabolism. However, there is conflicting evidence from different clinical trials of selenium supplementation in treating cardiometabolic diseases (CMDs). Objective: This meta-analysis aimed to identify the effects of selenium supplementation on insulin resistance, glucose homeostasis, and lipid profiles in patients with CMDs. Methods: Randomized controlled trials (RCTs) of selenium supplementation for treating CMDs were screened in five electronic databases. Insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG), and glycosylated hemoglobin A1C (HbA1c) were defined as the primary outcome markers, and lipid profiles were considered the secondary outcome markers. Results: Ten studies involving 526 participants were included in the meta-analysis. The results suggested that selenium supplementation significantly reduced serum insulin levels (standardized men difference [SMD]: −0.53; 95% confidence interval [CI] [−0.84, −0.21], p = 0.001, I² = 68%) and HOMA-IR (SMD: −0.50, 95% CI [−0.86, −0.14], p = 0.006, I² = 75%) and increased high-density lipoprotein cholesterol (HDL-C) levels (SMD: 0.97; 95% CI [0.26, 1.68], p = 0.007, I² = 92%), but had no significant effect on FPG, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C). Conclusion: Current evidence supports the beneficial effects of selenium supplementation on reducing insulin levels, HOMA-IR, and increasing HDL-C levels. Selenium supplementation may be an effective strategy for reducing insulin resistance in patients with CMDs. However, more high-quality clinical studies are needed to improve the certainty of our estimates.

Background: The dual burden of Type 2 Diabetes Mellitus (T2DM) and obesity is a critical public health issue. Low-carbohydrate diets have emerged as a potential intervention, yet clinical evidence remains inconclusive.Purpose: This meta-analysis assesses the impact of low-carbohydrate diets on metabolic profiles in overweight or obese T2DM patients, aiming to guide clinical practice.Methods: A systematic review identified randomized clinical trials (RCTs) comparing low-carbohydrate diets to control diets in T2DM patients from PubMed, Embase, and the Cochrane Library databases up to April 2023.Results: Seventeen RCTs, encompassing 1,197 participants, demonstrated that low-carbohydrate diets significantly improved HbA1c levels and fasting plasma glucose (mean difference [MD] = −0.36, 95% CI −0.44 to −0.29, p < 0.00001; MD = −10.71, 95% CI −14.39 to −7.03, p < 0.00001). They also reduced triglycerides and increased HDL cholesterol (MD = −19.91, 95% CI −28.83 to −10.99, p < 0.00001; MD = 2.49, 95% CI 1.07–3.91, p = 0.0006), without affecting LDL and total cholesterol. Weight loss, reduced BMI, lower diastolic blood pressure, and decreased waist circumference were additional benefits.Conclusion: Low-carbohydrate diets may enhance glycemic control and lipid profiles in overweight or obese T2DM patients, warranting consideration in T2DM management. However, the variability in diet definitions and methodologies underscores the necessity for further research to standardize dietary guidelines and evaluate long-term effects.

Endothelial injury, characterized by an inflammatory response and increased permeability, is an initial stage of atherosclerosis (AS). Adenosine 5-monophosphate (AMP), activated protein kinase (AMPK), and Nuclear Factor kappa B (NF-κB)/Yin Yang 1(YY1) signaling pathways play important roles in the process of endothelial injury. Berberine (BBR), a bioactive alkaloid isolated from several herbal substances, possesses multiple pharmacological effects, including anti-inflammatory, antimicrobial, antidiabetic, anticancer, and antioxidant activities. Previous studies showed a protective effect of berberine against endothelial injury. However, the underlying mechanism remains unclear. We explored the potential effect of BBR on TNF- (tumor necrosis factor-) α-induced injury of human umbilical endothelial cells (HUVECs) and studied its possible molecular mechanism. In the present study, HUVECs were divided into three groups. HUVEC viability was measured with Cell Counting Kit-8 assay. Extracellular lactic dehydrogenase (LDH) concentration was measured with LDH leakage assay. Endothelial microparticle (EMP) numbers were evaluated by flow cytometry analysis assay. The expression of proinflammatory cytokines was evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). The mRNA expression of NF-κB and YY1 was detected by Real-Time PCR (RT-PCR). The protein expression of NF-κB, YY1, and AMPK was detected by immunofluorescence microscopy assay or western blot analysis. The results showed that LDH concentration, EMPs numbers, and the expression of proinflammatory cytokines (IL-6, IL-8, and IL-1β) increased in TNF-α-induced injured HUVECs, but ameliorated by BBR pretreatment. BBR pretreatment upregulated the expression of phosphorylated AMPK and downregulated the expressions of NF-κB and YY1 in injured HUVECs induced by TNF-α, which were offset by the AMPK inhibitor Compound C (CC). The results indicated that BBR protected against TNF-α-induced endothelial injury via the AMPK/NF-κB/YY1 signaling pathway.