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Titolo:
Congestive heart failure induces endothelial cell apoptosis: Protective role of carvedilol
Autore:
Rossig, L; Haendeler, J; Mallat, Z; Hugel, B; Freyssinet, JM; Tedgui, A; Dimmeler, S; Zeiher, AM;
Indirizzi:
Univ Frankfurt, Dept Internal Med 4, Div Mol Cardiol, D-60590 Frankfurt, Germany Univ Frankfurt Frankfurt Germany D-60590 iol, D-60590 Frankfurt, Germany Hop Lariboisiere, IFR, INSERM U141, F-75475 Paris, France Hop Lariboisiere Paris France F-75475 INSERM U141, F-75475 Paris, France INSERM U143, Strasbourg, France INSERM U143 Strasbourg FranceINSERM U143, Strasbourg, France
Titolo Testata:
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
fascicolo: 7, volume: 36, anno: 2000,
pagine: 2081 - 2089
SICI:
0735-1097(200012)36:7<2081:CHFIEC>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; ELEVATED CIRCULATING LEVELS; NITRIC-OXIDE; CYTOCHROME-C; OXIDATIVE STRESS; FACTOR-ALPHA; DEATH; VASODILATION; MECHANISMS; PROTEASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Dimmeler, S Univ Frankfurt, Dept Internal Med 4, Div Mol Cardiol, Theodor Stern Kai 7,D-60590 Frankfurt, Germany Univ Frankfurt Theodor Stern Kai 7 Frankfurt Germany D-60590
Citazione:
L. Rossig et al., "Congestive heart failure induces endothelial cell apoptosis: Protective role of carvedilol", J AM COL C, 36(7), 2000, pp. 2081-2089

Abstract

OBJECTIVES The purposes of this study were to determine whether the serum of patients with congestive heart failure (CHF) can induce apoptosis of endothelial cells and to elucidate the underlying mechanisms. Moreover, the effect of the beta-blocker carvedilol was investigated. BACKGROUND Congestive heart failure is associated with impaired endothelial function in the peripheral systemic vasculature and with systemic releaseof inflammatory cytokines. Pro-inflammatory cytokines have been shown to induce endothelial cell apoptosis in vitro. Therefore, we hypothesized that CHF is associated with enhanced apoptosis of endothelial cells. METHODS Human umbilical vein endothelial cells were exposed to the serum of patients with CHF (n = 15) or healthy volunteers (n = 11), and apoptosis was determined by fluorescence staining of the nuclei and demonstration of deoxyribonucleic acid laddering. Moreover, apoptotic membrane particles were detected in plasma samples of patients with CHF. RESULTS The serum of patients with CHF revealed a significantly enhanced pro-apoptotic activity as compared with age- and gender-matched healthy volunteers (p < 0.001). Furthermore, patients with CHF revealed significantly elevated plasma concentrations of apoptotic membrane particles. Apoptosis ofendothelial cells correlated with elevated tumor necrosis factor-alpha (TNF-alpha) (r = 0.585, p = 0.002) and soluble TNF receptor serum levels (r = 0.517, p = 0.007). Carvedilol completely suppressed the increase in apoptosis induced by the serum of patients with CHF. Moreover, carvedilol dose-dependently inhibited TNF-alpha-induced apoptosis. The antiapoptotic activity of carvedilol was mediated by reduced activation of the caspase cascade through inhibition of mitochondrial cytochrome c release. The suppression of apoptosis by carvedilol was due to its antioxidative rather than beta-blocking effects, as the analogue BM91.0228, which has no beta-blocking activity,exerted similar effects. CONCLUSIONS These findings indicate that endothelial cell apoptosis may play a role in the pathophysiology of heart failure. Inhibition of endothelial cell apoptosis by carvedilol may contribute to the beneficial effects of carvedilol in patients with heart failure. (C) 2000 by the American Collegeof Cardiology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 20:43:24