Published online before print December 23, 2002, doi: 10.1161/01.CIR.0000045665.57256.86
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(Circulation. 2003;107:264.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Serum From Patients With Acute Coronary Syndromes Displays a Proapoptotic Effect on Human Endothelial Cells
A Possible Link to Pan-Coronary Syndromes
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.).
Correspondence to Prof Roberto Ferrari, Department of Cardiology, University of Ferrara c/o Arcispedale S Anna, Crso Giovecca 203, 44100 Ferrara, Italy. 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-
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).
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.
Key Words: apoptosis • inflammation • plaque • interleukins • endothelium
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