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 clinical sequelae. The proximate cause of plaque rupture is unknown. Accordingly, we investigated the potential role of the 92-kD gelatinase member of the matrix metalloproteinase family in acute coronary ischemia.


RESULTS
Coronary atherectomy specimens from patients with atherosclerosis and an acute ischemic syndrome consistent with recent plaque rupture (unstable angina) (n = 12) were immunostained for the presence of 92-kD gelatinase; the results were compared with those obtained by identical study of atherectomy specimens from patients with atherosclerosis 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, intracellular localization of enzyme (indicating active synthesis) was documented in 10 of 10 positively stained specimens from patients with unstable 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 immunostaining of adjacent sections.


CONCLUSIONS
92-kD gelatinase is commonly expressed in coronary arterial atherosclerotic lesions. Active synthesis 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.
Brown
D L
DL
Division of Cardiovascular Medicine, University of California, San Diego 92103-8411, USA.
Hibbs
M S
MS
Kearney
M
M
Loushin
C
C
Isner
J M
JM
D000787:Angina Pectoris / Q000201:enzymology / Q000601:surgery; D000789:Angina, Unstable / Q000201:enzymology* / Q000209:etiology / Q000601:surgery; D017225:Atherectomy, Coronary; D017364:Collagenases / Q000096:biosynthesis* / Q000502:physiology; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000601:surgery; D003331:Coronary Vessels / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000201:enzymology; D020780:Matrix Metalloproteinase 9; D009131:Muscle, Smooth, Vascular / Q000201:enzymology
D017364:Collagenases; D020780:Matrix Metalloproteinase 9