Matrix metalloproteinase expression in nonrheumatic aortic stenosis

Background: Nonrheumatic aortic stenosis (NAS) is considered to be a degene rative process characterized by valve thickening, fibrocalcific masses, col lagen disarray, and an inflammatory infiltrate. The matrix metalloproteinas es (MMPs) are a family of zinc- and calcium-dependent enzymes produced by i nflammatory cells that are capable of degrading collagen, elastin, and prot eoglycans. This study sought to test the hypothesis that MMPs are involved in the pathogenesis of NAS. Methods and Results: Aortic values were obtaine d from nine patients with NAS undergoing valve replace ment and from four p atients without NAS during autopsy. Microscopic analysis of NAS specimens r evealed variable areas of calcium deposits, fibrosis, and an extensive cell ular infiltrate consisting of macrophages, lymphocytes, and fibroblasts. Co ntrol aortic valves demonstrated normal architecture, a predominance of fib roblasts, occasional scattered macrophages, and no lymphocytes. Immunohisto chemical staining with antibodies to MMP-1, -2, -3 and -9 revealed expressi on of each enzyme in macrophages, lymphocytes, and fibroblasts of all NAS p atients. MMP-1; -2 and -3 were expressed by resident fibroblasts and macrop hages in normal valves, but to a lesser degree. Tc MMP-9 was not identified in normal valves. Conclusions: The current study confirms an inflammatory infiltrate composed of macrophages and lymphocytes in NAS. Additionally, th e increased expression of MMP-1, -2, and -3, along with the unique expressi on of MMP-9 in NAS valve leaflets was documented. These findings are consis tent with the hypothesis that NAS is associated with chronic inflammation a nd that the increased expression of MMPs may contribute to the pathogenesis of this disease process. Cardiovasc Pathol 2000;9:281-286 (C) 2000 by Else vier Science Inc.