Inflammation and plaque vulnerability.

Development of a thrombus at the site of an atherosclerotic plaque initiates abrupt arterial occlusion and is the proximate event responsible for the vast majority of acute ischemic syndromes. In nearly 75% of cases thrombus overlies a disrupted or ruptured plaque whereas the remainder of the thrombi overly an intact plaque with superficial endothelial erosion. Over the past several years, it has been recognized that plaque composition rather than plaque size or stenosis severity is important for plaque rupture and subsequent thrombosis. Ruptured plaques, and by inference, plaques prone to rupture, tend to be large in size with associated expansive arterial remodeling, thin fibrous cap with a thick or large necrotic lipid core with immuno-inflammatory cell infiltration in fibrous cap and adventitia and increased plaque neovascularity and intraplaque hemorrhage. The size of the necrotic lipid core and extent and location of plaque inflammation appear to be key factors in determining plaque instability. Inflammation and immune cell activation appears to play a key role in the loss of collagen in the fibrous cap, a prelude to fibrous cap rupture, through release of collagen degrading enzymes. Furthermore, inflammation may also play a key role in the death of collagen synthesizing smooth muscle cells which further contributes to loss of fibrous cap integrity. Inflammation also is likely a key player in the ensuing thrombosis that follows plaque disruption through the elaboration of the pro-coagulant protein, tissue factor. An improved understanding of the pathophysiology of plaque vulnerability and subsequent athero-thrombosis should provide novel insights into improved prevention of athero-thrombotic cardiovascular events.