Mechanisms of Atherosclerotic Plaque Instability

Cardiovascular disease (CVD) is the leading cause of mortality in humans worldwide. The main cause of CVD is the formation of thrombi due to by unstable atherosclerotic plaque rupture on the arterial wall. Long-term accumulation of thrombi results in vascular remodeling, and subsequent-stenosis of the lumen obstructs the blood flow, thereby leading to myocardial tissue ischemia and hypoxia. Sustained ischemia and hypoxia lead to myocyte necrosis, resulting in irreversible myocardial injury. Many molecular and cellular mechanisms are associated with atherosclerotic plaque instability (API). For example, macrophages can produce various inflammatory factors, adhesion factors, chemokines and matrix metalloproteinases (MMPs), which play important roles in the pathophysiological mechanisms of API and in maintaining plaque stability. These molecules may help predict unstable atherosclerotic plaques. If the plaque is stable, it will not be prone to rupture or thrombosis. Accordingly, in this review, we will discuss the different pathophysiological mechanisms of API and the related roles of macrophages in the mechanisms of API mainly in animal models and humans. We believe this review will provide a theoretical basis for the development of treatments and diagnostic approaches for the management of API.