Background: Nonrheumatic aortic stenosis (NAS) is considered to be a degenerative process characterized by valve thickening, fibrocalcific masses, collagen disarray, and an inflammatory infiltrate. The matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent enzymes produced by inflammatory cells that are capable of degrading collagen, elastin, and proteoglycans. This study sought to test the hypothesis that MMPs are involved in the pathogenesis of NAS. Methods and Results: Aortic values were obtained from nine patients with NAS undergoing valve replacement and from four patients without NAS during autopsy. Microscopic analysis of NAS specimens revealed variable areas of calcium deposits, fibrosis, and an extensive cellular infiltrate consisting of macrophages, lymphocytes, and fibroblasts. Control aortic valves demonstrated normal architecture, a predominance of fibroblasts, occasional scattered macrophages, and no lymphocytes. Immunohistochemical staining with antibodies to MMP-1, -2, -3 and -9 revealed expression of each enzyme in macrophages, lymphocytes, and fibroblasts of all NAS patients. MMP-1, -2 and -3 were expressed by resident fibroblasts and macrophages in normal valves, but to a lesser degree. MMP-9 was not identified in normal valves. Conclusions: The current study confirms an inflammatory infiltrate composed of macrophages and lymphocytes in NAS. Additionally, the increased expression of MMP-1, -2, and -3, along with the unique expression of MMP-9 in NAS valve leaflets was documented. These findings are consistent with the hypothesis that NAS is associated with chronic inflammation and that the increased expression of MMPs may contribute to the pathogenesis of this disease process. (C) 2000 by Elsevier Science Inc.