Serum From Patients With Acute Coronary Syndromes Displays a Proapoptotic Effect on Human Endothelial Cells

Abstract

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 (nϭ32; group 2) or acute coronary syndromes (nϭ41; 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 (14Ϯ6%) than in group 2 (3.3Ϯ1.8%) and group 1 (1.35Ϯ0.8%) (PϽ0.001). Fas and Bcl-2 were increased in group 3 with respect to groups 1 and 2 (PϽ0.01). 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 Ͻ50%. The percentage of apoptosis in group 3 significantly correlated to the numbers of coronary complex lesions at angiography (rϭ0.58, PϽ0.0005). In group 3, apoptosis and the Bax/Bcl-2 ratio decreased at 1 year (PϽ0.0001, PϽ0.05 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.

ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT

“…We have previously reported that serum from patients with acute coronary syndromes (ACS) exerts a pro-apoptotic effect on the endothelium, thus contributing to plaque instability [23]. The results of the current study are the first ones in patients with stable CAD and suggest that even during the chronic stable phases of the disease the endothelium has abnormalities.…”

“…The most interesting evidence of a possible beneficial effect of perindopril on the endothelium comes from the results at cellular level in which we used a previously validated methodology [23] that allows the measurement of the harder end point of endothelial function. The data suggest that serum from CAD patients is pro-apoptotic and induces a down-regulation of eNOS protein expression and activity.…”

CD34 + and Endothelial Progenitor Cells in Patients With Various Degrees of Congestive Heart Failure

“…12 VEGF, stromal derived factor-1 (SDF-1), granulocyte-colony stimulating factor, and B-type natriuretic peptide (BNP) were measured by ELISA (R&D) and by a solid-phase immunoradiometric assay (Shionoria), respectively.…”

Tumor Necrosis Factor-α Receptor 1 Is a Major Predictor of Mortality and New-Onset Heart Failure in Patients With Acute Myocardial Infarction

“…TNF-␣, sTNFR-1, sTNFR-2, IL-6, and IL-1ra were measured as previously described, 3,7 with sensitivity and intra-assay and interassay variabilities of 3 pg/mL, Ͻ5.2%, and Ͻ9.9%; 3 pg/mL, Ͻ2.9%, and Ͻ8.8%; 1 pg/mL, Ͻ2.5%, and Ͻ5.1%; 0.7 pg/mL, Ͻ4.2%, and Ͻ6.4%; and 22 pg/mL, Ͻ3.1%, and Ͻ5%, respectively. IL-10 was quantified by Quantikine Immunoassay by R&D with an intra-and inter-assay variabilities of Ͻ5% and 8%, respectively, and a sensitivity of Ͻ3.9 pg/mL.…”

“…6 Several cytokines, particularly those belonging to the TNF family members, are known to be elevated during MI, 7 but their role in predicting subsequent prognosis remains to be addressed. Therefore, our primary aim was to undertake a systematic evaluation of TNF-␣ and its type 1 (sTNFR-1) and 2 (sTNFR-2) soluble receptors, together with interleukin (IL)-6, IL-1 receptor antagonist (ra), and IL-10, in a consecutive series of MI patients and to correlate them to short-and long-term incidence of death and HF.…”