Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques.

Abstract

Dysregulated extracellular matrix (ECM) metabolism may contribute to vascular remodeling during the development and complication of human atherosclerotic lesions. We in- vestigated the expression of matrix metalloproteinases (MMPs), a family of enzymes that degrade ECM compo- nents in human atherosclerotic plaques (n =30) and in uninvolved arterial specimens (n=11). We studied members of all three MMP classes (interstitial coilagenase, MMP-1; gel- atinases, MMP-2 and MMP-9; and stromelysin, MMP-3) and their endogenous inhibitors (TIMPs 1 and 2) by immu- nocytochemistry, zymography, and immunoprecipitation. Normal arteries stained uniformly for 72-kD gelatinase and TIMPs. In contrast, plaques' shoulders and regions of foam cell accumulation displayed locally increased expression of 92-kD ge