Effects Of Cell Apoptosis Induced By TNF-α,No In Congestic Heart Failure And Intervention Of Carvedilol

OBJECTIVE The clinic study is to explore the changes and interrelations of TNF-a NO and sFas in the plasma of patients with chronic congestic heart failure . The purposes of the basic study are to determine whether TNF-a can induce apoptosis of endothelial cells and to explore the relations of TNF-a NCK sFas and apoptosis . Moreover, the effect of the beta-blocker carvedilol is investigated .And we may elucidate the underlying mechanisms. METHODS1 .The blood samples were taken from eighty patients and twenty healthy subjects.Plasma TNF-a was measured by RIA;Plasma NO was assessed with revert enzymetic means of nitric acid ;sFas was measured by ELISA.2.Human vein endothelial cells were exposed to TNF-a and apoptosis was determined by FCM .NO and sFas in supernatant were detected accordingly;3.Human vein endothelial cells were exposed to carvedilol + TNF-a, or atenolol + TNF-a and apoptosis was determined by FCM .NO and sFas in supernatant were detected accordingly. RESULTS1.The levels of plasma TNF-a NO and sFas were significantly higher in CHF patients than those in healthy subjects and increased with the severity of heart failure The levels of TNF-a NO and sFas showed significant relation with each other and all of them were closelyrelated to the ejection fraction.2.TNF-a induced the apoptosis of endothelial cells.The concentrations of NO sFas and apoptosis of endothelial cells correlated with the level of TNF-a and the exposed time.3.L-NAME blocked the production of NO and reduced the number of apoptotic cells.4.Carvedilol partly suppressed the cell apoptosis induced by TNF-a and the production of NO had no changes.CONCLUSIONSl.The elevated plasma concentrations of TNF-a can induce cell apoptosis of cardiac muscle and vascular endothelium . Cell apoptosis may play a role in the remodeling of ventricle and vascular .2.Cell apoptosis and other negative effects to heart induced byTNF-a may follow this route: TNF- a →......→ iNOS→NO→......→sFas→......→ apoptosis.3.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. The potent antioxidant effect of carvedilol is probably responsible for the superior effect.