Effects of nebivolol on proliferation and apoptosis of human coronary artery smooth muscle and endothelial cells

Objective: Secondary failure due to late restenosis continues to occur in 30-50% of individuals after PTCA. beta -Blockers play an important role in the treatment of CAD. The aim of this study was to investigate the effects of the new beta -blocker nebivolol on cell proliferation of human coronary smooth muscle cells (haCSMCs) and endothelial cells (haECs) in comparison to traditional beta -blockers. Methods: The effect of nebivolol and other beta -blockers on proliferation of HaECs and HaCSMCs was analyzed by bromodeoxyuridine incorporation. Apoptosis was measured by determination of hypodiploid DNA in both cell types. Additionally, in HaECs NO formation, endothelin-1 transcription and secretion were determined. Results: Incubation for 1, 2, 4, 7 or 14 days resulted in a concentration- and time-dependent reduction of proliferation up to 80% in HaECs and HaCSMCs. beta -Blockers such as propranolol, metoprolol or bisoprolol did not exert this effect. Nebivolol inhibited accelerated haCSMC proliferation even in the presence of growth factors such as TGF beta (1) and PDGF-BB. Nebivolol concentration-dependently induced a moderate apoptosis (10(-5) mol/1: 238) and a decrease of haCSMCs in the S-phase by 66%. HaECs showed comparable results. During nebivolol incubation NO formation of HaCEs increased, while endothelin-1 transcription and secretion were suppressed. Conclusion: Whereas classical beta -blockers do not affect cell growth, only nebivolol inhibits haCSMC or haEC proliferation and induces a moderate rate of apoptosis. Furthermore, in HaCEs NO formation increases and endothelin-1 secretion decreases suggesting that nebivolol may represent a beta -blocker with great promises in CAD therapy. (C) 2001 Elsevier Science BN. All rights reserved.