The Role of Collagenases in the Pathogenesis of Vulnerable Atherosclerotic Plaques(<特集>動脈硬化と細胞外マトリックス)

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Acute coronary syndromes including acute myocardial infarction, unstable angina, and cardiac sudden death are often triggered by rupture of the vulnerable atherosclerotic plaque. Among various extracellular matrices, interstitial collagen plays a key role in the mechanical strength of the artery. Members of the matrix metalloproteinase (MMP) family produced by macrophages, in particular interstitial collagenases (MMP-1 /collagenase-1, MMP-8/collagenase-2, MMP-13/collagenase-3), likely contribute to plaque vulnerability. Recent clinical trials have demonstrated that lipid lowering with statins reduces the onset of the acute coronary syndromes in patients despite only modest reduction in stenoses detected by angiography, thus suggesting the possibility that lipid lowering prevents coronary events mainly by reducing plaque vulnerability ("stabilization") rather than merely shrinking the plaque burden ("regression"). Preclinical studies including our own support this concept of plaque stabilization. We have shown in hypercholesterolemic rabbits that lipid lowering by either diet or statin treatment reduces a number of features typical of the "vulnerable" plaque : oxidative stress, endothelial cell dysfunction, smooth muscle cell activation, and macrophage infiltration. An inverse relationship between reduced MMP-1/collagenase-1 and increased collagen in the intima of rabbit aorta suggests the important role of collagenase action in collagen metabolism in atheroma. However, further studies are needed to address direct in vivo evidence that links action of the MMP family collagenases with regulation of the collagen content of atheroma, critical to the clinical complications of coronary atherosclerosis.
日本結合組織学会の論文
2002-12-25

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