Abstract
Matrix metalloproteinase-9 (MMP-9) belongs to the MMP family and has been widely investigated. Excessive MMP-9 expression can enhance extracellular matrix degradation and promote plaque instability. Studies have demonstrated that MMP-9 levels are higher in vulnerable plaques than in stable plaques. Additionally, several human studies have demonstrated that MMP-9 may be a predictor of atherosclerotic plaque instability and a risk factor for future adverse cardiovascular and cerebrovascular events. MMP-9 deficiency or blocking MMP-9 expression can inhibit plaque inflammation and prevent atherosclerotic plaque instability. All of these results suggest that MMP-9 may be a useful predictive biomarker for vulnerable atherosclerotic plaques, as well as a therapeutic target for preventing atherosclerotic plaque instability. In this review, we describe the structure, function, and regulation of MMP-9. We also discuss the role of MMP-9 in predicting and preventing atherosclerotic plaque instability.
Highlights
Vulnerable plaques are a leading cause of acute coronary syndrome and sudden death
Vulnerable plaques are characterized as those having a thin fibrous cap, a large lipid pool, and infiltration of inflammatory cells
Numerous studies have demonstrated that Matrix metalloproteinase-9 (MMP-9) levels are higher in vulnerable plaques than in stable plaques, and high circulating levels of Matrix metalloproteinases (MMPs)-9 are closely related to adverse cardiovascular and cerebrovascular events [48, 53, 62, 141,142,143]
Summary
Studies have shown that 75% of acute coronary syndrome cases are caused by plaque rupture [1, 2]. Mature plaques mainly comprise endothelial cells (ECs), vascular smooth muscle cells (VSMC), macrophages, and a fibrous cap containing extracellular matrix (ECM) components [6]. Among these components, the ECM plays an especially important role in plaque stability [7]. Histopathological studies showed that MMP-9 was mostly distributed in the shoulder regions, necrotic core, and the fibrous cap of the atherosclerotic plaques, and that MMP-9 levels and activity were higher in unstable plaques than in stable plaques [13,14,15,16]. This review will explore the function of MMP-9 in vulnerable plaques and primarily discuss the predictive and preventive value of MMP-9 in atherosclerotic plaque instability
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