Role of smooth muscle cell death in advanced coronary primary lesions: implications for plaque instability

Objective: Instability of coronary atheroma leads to the onset of acute cor onary syndromes including myocardial infarction and death, as well as to th e progression of the arteriosclerotic disease. As yet, the underlying facto rs and mechanisms causing plaque rupture are not completely understood. Sin ce a low content of smooth muscle cells (SMCs) apparently plays a key role, the question points to the events leading to the loss of intimal SMCs. Met hods: We compared coronary atherectomy specimens from 25 patients with unst able angina to those from 25 patients with stable angina. Transmission elec tron microscopy was used to identify intimal cell population, to detect sta ge and cell type of apoptosis, and to differentiate between apoptosis and n ecrosis. Results: plaques associated with unstable angina contained more ma crophages/lymphocytes and significantly less SMCs (P=0.01), compared with s table angina plaques. Specific cell death forms, apoptosis and necrosis, we re present in all coronary atheroma. As key findings, both the proportion o f SMCs undergoing apoptosis and the frequency of cytoplasmic remnants of ap optotic SMCs (matrix vesicles) were significantly increased in unstable ver sus stable angina lesions (P=0.002 and P=0.002). In addition, cellular necr osis was more frequent in the first coronary atheroma group (P=0.02). Posit ive correlations were found between the frequency of apoptotic cells and ne crosis (r=0.41, P=0.04), and that of matrix vesicles and necrosis (r=0.63, P=0.001) only in plaques with unstable angina, but not in those with stable angina. Conclusions: Our data demonstrate that high cell death due to apop tosis and necrosis is a basic in situ feature found in advanced coronary pr imary lesions associated with unstable angina, possibly explaining their lo w density of (viable) SMCs. Thus, antagonization of intimal cell death shou ld be considered in order to stabilize the intimal plaque texture of corona ry atheroma with the ultimate goal to prevent plaque rupture. (C) 1999 Else vier Science B.V. All rights reserved.