Myeloperoxidase and plaque vulnerability.

Inflammation and the Vulnerable Plaque Sudden cardiac death remains the leading cause of mortality in industrialized societies, outpacing all cancer related deaths combined. The majority of sudden cardiac deaths arise from acute myocardial infarction secondary to intracoronary artery thromboses. Remarkably, the culprit lesions involved are typically not flow-limiting stenoses,1,2 but rather inflamed lipid-laden lesions.3,4 Whereas plaque fissuring or rupture, which exposes the intensely prothrombogenic lipid core, occurs in a majority of cases, fully 40% of intracoronary artery thromboses arise at sites of superficial erosions, where endothelial cell (EC) loss and denudation occurs.3 The mechanisms responsible for plaque vulnerability leading to acute coronary artery thrombosis remain poorly understood. Mounting evidence, however, points toward a critical role for inflammatory processes.5–8 Macrophages serve as the dominant cell type in the immediate site of both plaque ruptures and superficial erosions in subjects who experience acute coronary thrombosis,8 and recent clinical investigations reveal important associations between leukocytes,9,10 their enzymes,11–13 and their activation,14,15 in subjects with unstable angina and acute coronary syndromes. In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Sugiyama and colleagues significantly extend our knowledge of potential pathophysiologic inflammatory processes within vulnerable atheroma.16 Using a combination of biochemical, cellular, and immunohistologic studies, they describe unifying mechanistic links between the activity of the leukocyte enzyme myeloperoxidase (MPO) and two cardinal features of vulnerable plaque: EC loss/denudation and development of a prothrombotic phenotype.