Coronary artery disease (CAD) is a caused by atherosclerotic plaque buildup in the coronary arteries that supply blood and oxygen to the heart. Matrix metalloproteinase (MMP) is a family of zinc-dependent endopeptidase that is involved in various stages of atherosclerosis as demonstrated in in vitro and in vivo studies. MMP-2 is associated with both stable and unstable atherosclerotic plaque formation. The current review aimed to identify the role of MMP-2 in atherosclerosis development among CAD patients. Literature search was conducted through four online databases and only studies that were published from 2018 until February 2023 were included. The risk of bias was assessed by using the NewcastleOttawa Scale. A total of 10,622 articles were initially identified, and only eight studies that fulfilled the selection criteria were included in this review. The results showed that MMP-2 levels and activity were higher in patients with unstable CAD than those with stable CAD and healthy subjects. There was a significant association between MMP-2 levels and cardiovascular disease with MMP-14 levels, which is a pro-MMP-2 activator. In addition, two single nucleotide polymorphisms of the MMP-2 gene (rs243865 and rs243866) were significantly associated with the development of atherosclerosis. In conclusion, MMP-2 plays a crucial role in the development of atherosclerosis among patients with CAD and could be a potential target for CAD therapy.

Coronary artery disease (CAD) is the leading cause of death globally and is a heart condition involving insufficient blood supply to the heart muscle due to atherosclerotic plaque formation. Atherosclerosis is a chronic disease in which plaques, made up of fat, cholesterol, calcium, and other substances, build up on the inner walls of arteries. Recently, there has been growing interest in finding reliable biomarkers to understand the pathogenesis and progression of atherosclerosis. Tissue Inhibitors of Metalloproteinases (TIMPs) have emerged as potential candidates for monitoring atherosclerotic development. TIMPs are a family of endogenous proteins that regulate matrix metalloproteinases (MMPs), enzymes involved in remodeling the extracellular matrix. A systematic search using Prisma guidelines was conducted and eleven studies were selected from four different databases: Web of Science (WOS), Scopus, Ovid, and PubMed. The Newcastle–Ottawa Scale (NOS) score was used to assess the risk of bias for each study. A meta-analysis was performed, and the hazard ratio (HR) and its 95% confidence interval (CI) were determined. Among the eleven studies, six reported a positive association between higher levels of TIMPs and an increased risk of atherosclerosis. Conversely, four studies support low TIMPs with high CAD risk and one study showed no significant association between TIMP-2 G-418C polymorphism and CAD. This divergence in findings underscores the complexity of the relationship between TIMPs, atherosclerosis, and CAD. In addition, a meta-analysis from two studies yielded a HR (95% CI) of 1.42 (1.16–1.74; p < 0.001; I² = 0%) for TIMP-2 in predicting major adverse cardiovascular events (MACEs). In conclusion, the existing evidence supports the notion that TIMPs can serve as biomarkers for predicting the severity of atherosclerosis, myocardial damage, and future MACEs among CAD patients. However, further exploration is warranted through larger-scale human studies, coupled with in vitro and in vivo investigations.

INPLASY202470070 Unveiling TIMPs: A Systematic Review of Their Role as Biomarkers in Atherosclerosis and Coronary Artery Disease Keywords: Tissue inhibitor of metalloproteinases; atherosclerosis; I…

Cardiovascular disease (CVD) remains a leading cause of mortality globally, underscoring the need for robust predictive biomarkers to enhance risk stratification. Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has emerged as a promising biomarker linked to oxidative stress and endothelial dysfunction, both critical mechanisms in atherogenesis and cardiovascular events. Objectives: This study aimed to evaluate the prognostic value of sLOX-1 in predicting major adverse cardiovascular and cerebrovascular events (MACCEs), myocardial infarction (MI), heart failure (HF), and stroke outcomes through a systematic review and meta-analysis. Methods: A systematic literature search was conducted across PubMed, Scopus, Web of Science, and Ovid databases for studies published between 2014 and October 2024. Eligible studies assessed the association between sLOX-1 levels and future CVD outcomes in adult populations. Meta-analysis pooled hazard ratios (HRs) were assessed using random- and fixed-effects models. Heterogeneity was evaluated using the I² statistic, and study quality was assessed using the Newcastle–Ottawa Scale. Results: Fourteen studies were included, encompassing diverse populations with coronary artery disease (CAD), acute coronary syndrome (ACS), or stroke, with follow-up durations ranging from 30 days to 19.5 years. The meta-analysis of three studies on CAD patients demonstrated a significant association between elevated sLOX-1 levels and increased MACCE risk (HR: 2.3, 95% CI: 0.99–5.33, p = 0.05), albeit with high heterogeneity (I² = 83%). The fixed-effects analysis yielded a more consistent HR of 1.47 (95% CI: 1.19–1.81, p < 0.01). Conclusions: sLOX-1 shows promising potential as a prognostic biomarker for CVD and is associated with an increased risk of MACCEs in CAD patients. However, the high heterogeneity among the included studies highlights the need for standardized protocols and larger, well-designed prospective studies to validate its clinical utility. The integration of sLOX-1 into risk prediction models could improve CVD management by identifying high-risk individuals for targeted interventions.

INPLASY2024120078 Prognostic value of lectin-like oxidized LDL receptor-1 for future CVD risk and outcome: Systematic review and meta-analysis Keywords: Cardiovascular disease; coronary artery dise…

Acute Coronary Syndrome (ACS) is a severe manifestation of Coronary Artery Disease (CAD) caused by the rupture of unstable atherosclerotic plaques, resulting in reduced myocardial blood flow. Smoking is a major risk factor for ACS and has been associated with increased matrix metalloproteinase (MMP) activity, which contributes to the degradation of the plaque fibrous cap. However, the molecular alterations associated with smoking in ACS remain incompletely understood. This study aimed to investigate the expression of α1nAChR, ERK1/2, and c-FOS genes, together with MMP protein levels in atherosclerotic plaque tissues and peripheral blood mononuclear cells (PBMCs) of CAD patients. A total of 41 atherosclerotic plaque samples (26 smokers, 15 non-smokers) and 180 clinical subjects [n = 30 per group: ACS, chronic coronary syndrome (CCS), and controls; smokers and non-smokers] were included. Gene expression of ⍺1nAChR, ERK 1/2, and c-FOS was analyzed by RT-qPCR, while protein levels of MMP-2, MMP-9, and TIMP 3 were measured using ELISA. The expression of ERK 1/2 and c-FOS were significantly higher in plaque tissues of smokers compared with non-smokers (1.671- and 1.327-fold; p < 0.05). In PBMCs, α1nAChR expression was higher in CCS smokers (1.383-fold), while ERK 1/2 expression was higher in ACS smokers (1.355-fold). MMP-9 levels were significantly elevated in ACS and CCS compared with controls (p < 0.001). In conclusion, smoking CAD patients demonstrated increased expression of α1nAChR, ERK and MMP-9, indicating smoking-associated alterations in ⍺1nAChR-ERK signaling-related biomarkers in ACS.