Unveiling TIMPs: A Systematic Review of Their Role as Biomarkers in Atherosclerosis and Coronary Artery Disease

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; I-2 = 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.