IDENTIFICATION OF 92-KD GELATINASE IN HUMAN CORONARY ATHEROSCLEROTIC LESIONS - ASSOCIATION OF ACTIVE ENZYME-SYNTHESIS WITH UNSTABLE ANGINA

Background Acute coronary ischemia is usually initiated by rupture of atherosclerotic plaque, leading to intracoronary thrombosis and clinic al sequelae. The proximate cause of plaque rupture is unknown. Accordi ngly, we investigated the potential role of the 92-kD gelatinase membe r of the matrix metalloproteinase family in acute coronary ischemia. M ethods and Results Coronary atherectomy specimens from patients with a therosclerosis and an acute ischemic syndrome consistent with recent p laque rupture (unstable angina) (n=12) were immunostained for the pres ence of 92-kD gelatinase; the results were compared with those obtaine d by identical study of atherectomy specimens from patients with ather osclerosis and angina but without acute ischemia (stable angina) (n=12 ). Positive immunostaining for 92-kD gelatinase was present in 83% of specimens from both unstable and stable angina patients. However, intr acellular localization of enzyme (indicating active synthesis) was doc umented in 10 of 10 positively stained specimens from patients with un stable angina compared with 3 of 10 positively stained specimens from patients with stable angina. Macrophages and smooth muscle cells were the major sources of 92-kD gelatinase in all specimens examined by imm unostaining of adjacent sections. Conclusions 92-kD gelatinase is comm only expressed in coronary arterial atherosclerotic lesions. Active sy nthesis of 92-kD gelatinase by macrophages and smooth muscle cells in atherosclerotic lesions may play a pathogenic role in the development of acute coronary ischemia.