Vascular biology of collagenases in vulnerable atherosclerotic plaques

摘要

Disruption of the vulnerable atherosclerotic plaque often triggers acute coronary syndromes including acute myocardial infarction, unstable angin,and cardiac sudden death. Interstitial collagen may play a critical role in the mechanical strength of the artery Members of the matrix metalloproteinase (MMP) family produced by macrophages, particularly interstitial collagenases (MMP-1/collagenase-1, MMP-8/collagenase-2, and MMP-13/collagenase-3), likely contribute to plaque vulnerability Recent preclinical and clinical studies have suggested that lipid lowering prevents coronary events by reducing plaque vulnerability ("stabilization") rather than merely shrinking the atheroma burden ("regression").We have shown in hypercholesterolemic rabbits that lipid lowering by either diet alone or statin treatment can reduce a number of features typical of the vulnerable plaque An inverse relationship between reduced MMP-l/collagenase-1 and increased collagen in rabbit atheromata suggests the important role of collagenase action in collagen metabolism in atheromata However, further studies are needed to address direct in vivo evidence that links collagenase action with regulation of the plaque collagen, critical to the clinical complications of coronary atherosclerosis.