Aminuddin Amilia, Samah Nazirah, Vijakumaran Ubashini, Che Roos Nur Aishah, Nor Faridah Mohd, Wan Razali Wan Mohammad Hafiz, Mohamad Shawal Faizal, Cong Beh Boon, Hamzah Faizal Amri, Hamid Adila A, Ugusman Azizah
Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia.
Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia.
Diseases. 2024 Aug 2;12(8):177. doi: 10.3390/diseases12080177.
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; < 0.001; = 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.
冠状动脉疾病（CAD）是全球主要的死亡原因，是一种由于动脉粥样硬化斑块形成导致心肌供血不足的心脏疾病。动脉粥样硬化是一种慢性疾病，由脂肪、胆固醇、钙和其他物质组成的斑块在动脉内壁堆积。最近，人们越来越有兴趣寻找可靠的生物标志物来了解动脉粥样硬化的发病机制和进展。金属蛋白酶组织抑制剂（TIMPs）已成为监测动脉粥样硬化发展的潜在候选物。TIMPs是一类内源性蛋白质家族，可调节基质金属蛋白酶（MMPs），这些酶参与细胞外基质的重塑。使用Prisma指南进行了系统检索，从四个不同的数据库中选择了11项研究：科学网（WOS）、Scopus、Ovid和PubMed。使用纽卡斯尔-渥太华量表（NOS）评分来评估每项研究的偏倚风险。进行了荟萃分析，并确定了风险比（HR）及其95%置信区间（CI）。在这11项研究中，6项报告TIMPs水平较高与动脉粥样硬化风险增加之间存在正相关。相反，4项研究支持低水平的TIMPs与高CAD风险相关，1项研究表明TIMP-2 G-418C多态性与CAD之间无显著关联。这些研究结果的差异凸显了TIMPs、动脉粥样硬化和CAD之间关系的复杂性。此外，两项研究的荟萃分析得出TIMP-2预测主要不良心血管事件（MACEs）的HR（95%CI）为1.42（1.16-1.74；<0.001；I²=0%）。总之，现有证据支持TIMPs可作为预测CAD患者动脉粥样硬化严重程度、心肌损伤和未来MACEs的生物标志物这一观点。然而，需要通过大规模的人体研究以及体外和体内研究进行进一步探索。
