Expression Of Vascular Matrix Metalloproteinases And Their Inhibitors And Induction Of Apoptosis By Tumor Necrosis Factor Alpha In Human Aortic Smooth Muscle Cells

[Background]Disease caused by atherosclerosis is the main public health problem in world-wide range. Acute coronary syndrome (ACS), including unstable angina, acute myocardial infaction and ischemic sudden death, are the leading cause of death in the industrialized world. It is of paramount significance to explore the underlying pathophysiological mechanism for the prevention and treatment of ACS. Acute coronary thrombus formation secondary to vulnerable atherosclerotic plaque is the main pathological basis of ACS. Smooth muscle cells (SMCs) are the major cell type of medium- and large-sized blood vessels. These cells synthesize important components of the extracellular matrix (ECM), including collagens, elastin, and proteoglycans. SMCs not only can produce the bulk of the ECM of the vessels, but also can produce tissue inhibitor of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs), while the latter could selectively digest the individual components of ECM. By overexpressing MMPs, vulnerable atherosclerotic plaque plays an important role in fibrous cap destruction and new blood vessel formation, the processes that have great relevance to plaque stability. However, little is known about the mechanisms of controlling enhanced expression of MMPs. Meanwhile, apoptosis in SMCs has been proposed to be importantly involved in the neointimal thickening and plaque stability. A high level of apoptotic cell death might impair the maintenance of the matrix scaffolding of the fibrous cap of the plaque and thus predispose to plaque rupture. The signals that induce these processes remain obscure. It has been found by pathological investigation that the development of advanced plaque is marked by a considerable inflammatory infilatrate, with cells of monocyte lineage being...