on December 23, 2002
Published online before print December 23, 2002, doi: 10.1161/01.CIR.0000045665.57256.86
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Submitted on August 6, 2002
From the Department of Cardiology, University of Ferrara, Ferrara, Italy (M.V., F.M., E.M., R.P., G.G., R.F.); Salvatore Maugeri Foundation, Cardiovascular Pathophysiology, Research Centre, Gussago (BS), Italy (M.V., L.A., S.C., L.C., G.F., R.F.); and the Department of Pathologic Anatomy, Spedali Civili, Brescia, Italy (P.G.G.). * To whom correspondence should be addressed. E-mail: fri{at}dns.unife.it.
Background—Endothelial apoptosis of atherosclerotic lesions is a possible determinant for the stable-to-vulnerable plaque transition. Recent data support the notion that plaque activation may be a pan-coronary process, advocating the existence of circulating triggers. Methods and Results—Serum from 40 healthy subjects (group 1) and 73 patients with stable angina (n=32; group 2) or acute coronary syndromes (n=41; group 3) was incubated with human umbilical vein endothelial cells. The percentage of apoptosis by flow cytometry and Fas, Bax, and Bcl-2 protein expression by immunoblotting were evaluated at entry in patients and control subjects and repeated after 12 months in group 3. At baseline, apoptotic nuclei were higher in group 3 (14±6%) than in group 2 (3.3±1.8%) and group 1 (1.35±0.8%) (P<0.001). Fas and Bcl-2 were increased in group 3 with respect to groups 1 and 2 (P<0.01). Coincubation of group 3 serum with anti-tumor necrosis factor- Conclusions—Serum from patients with acute coronary syndromes displays a proapoptotic effect on human endothelial cells, supporting the theory of the existence of circulating triggers potentially able to activate atherosclerotic lesions.
Revised on September 30, 2002
Accepted on October 1, 2002
Serum From Patients With Acute Coronary Syndromes Displays a Proapoptotic Effect on Human Endothelial Cells. A Possible Link to Pan-Coronary Syndromes
Marco Valgimigli MD,
and anti-interleukin-6 monoclonal antibodies did not affect the human umbilical vein endothelial cell apoptotic process, whereas addition of Trolox decreased apoptosis to <50%. The percentage of apoptosis in group 3 significantly correlated to the numbers of coronary complex lesions at angiography (r=0.58, P<0.0005). In group 3, apoptosis and the Bax/Bcl-2 ratio decreased at 1 year (P<0.0001, P<0.05 respectively).
Key words: apoptosis • inflammation • plaque • interleukins • endothelium
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