The stromelysins are members of a family of extracellular matrix metalloproteinases. These enzymes may erode the connective tissue in atherosclerotic plaques, leading to fissuring and acute thrombotic events. Cell-specific stromelysin expression in human atherosclerotic plaques was studied by in situ hybridization and Immunocytochemistry. Sections were taken from nine coronary arteries: eight with wellestablished plaques and one normal. Unambiguous signals were seen in five plaques, two were inconclusive, and the remaining sample was negative, as was the normal coronary artery. Stromelysin mRNA transcripts were localized to isolated individual cells, some ofwhich were smooth muscle, in the plaque cap, intima, and adventitia, but not the media. Expression was also seen in large clusters of macrophages that contained intracellular lipid deposits. The isolated expression of stromelysin by smooth muscle cells may reflect local connective tissue remodeling associated with growth and the formation of the plaque, whereas the more extensive expression associated with macrophages may be of greater pathological sinficance, contributing to the destabilization of the extracellular matrix and eventual plaque rupture.The morphology of atheromatous plaques ranges from solid fibrous structures to those with a substantial lipid core, covered by a fibrous cap (1). Fibrous plaques are essentially stable lesions, but the "soft," lipid-laden plaques are prone to intimal tearing (fissuring), the commonest event initiating coronary thrombosis (2). Migration of macrophages and T cells into soft plaques has been observed, and the lesion has all the hallmarks of an inflammatory response (3). As macrophages produce a number of potent proteases (4), their presence in large numbers may lead to plaque rupture as a result of destabilization of the supporting connective tissue matrix. Alternatively, cytokines and growth factors secreted by activated macrophages (5) may induce neighboring cells, such as smooth muscle cells, to erode the collagen and elastin that forms the framework of the plaque.Stromelysins are a group of enzymes within the mammalian tissue metalloproteinase (MP) family. These proteinases are generally characterized by their ability to function at neutral pH, the need to bind Zn2+ as a cofactor, and their secretion in a latent form requiring activation for proteolytic activity (6, 7). As a group, the tissue MPs have the capacity to completely degrade all extracellular matrix macromolecules, playing a major role in both physiological and pathological events that lead to matrix degradation. Stromelysins are produced by a variety ofcell types, have a broad substrate specificity, and can degrade most of the constituents of the extracellular matrix within atherosclerotic plaques. Stromelysins 1 and 2 have an identical spectrum of activity (reviewed in refs. 6 and 8), but stromelysin 1 is more potent (9). The principal substrate is proteoglycan core protein, but these enzymes also degrade nonhelical regions of types II, IV,...