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 3 0-50% of individuals after PTCA. beta -Blockers play an important role in t he treatment of CAD. The aim of this study was to investigate the effects o f the new beta -blocker nebivolol on cell proliferation of human coronary s mooth muscle cells (haCSMCs) and endothelial cells (haECs) in comparison to traditional beta -blockers. Methods: The effect of nebivolol and other bet a -blockers on proliferation of HaECs and HaCSMCs was analyzed by bromodeox yuridine incorporation. Apoptosis was measured by determination of hypodipl oid 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 reductio n of proliferation up to 80% in HaECs and HaCSMCs. beta -Blockers such as p ropranolol, metoprolol or bisoprolol did not exert this effect. Nebivolol i nhibited accelerated haCSMC proliferation even in the presence of growth fa ctors 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 i ncubation NO formation of HaCEs increased, while endothelin-1 transcription and secretion were suppressed. Conclusion: Whereas classical beta -blocker s do not affect cell growth, only nebivolol inhibits haCSMC or haEC prolife ration and induces a moderate rate of apoptosis. Furthermore, in HaCEs NO f ormation increases and endothelin-1 secretion decreases suggesting that neb ivolol may represent a beta -blocker with great promises in CAD therapy. (C ) 2001 Elsevier Science BN. All rights reserved.