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

  • Cardiovasc Res. 2001 Feb 1;49(2):430-9. doi: 10.1016/s0008-6363(00)00253-4.
B R Brehm  1 ,  S C Wolf ,  D Bertsch ,  M Klaussner ,  S Wesselborg ,  S Schüler ,  K Schulze-Osthoff
Affiliations
  • 1. Department of Cardiology, University of Tübingen, Otfried-Müllerstrasse 10, 72076, Tübingen, Germany. [email protected]
PMID: 11164853 DOI: 10.1016/s0008-6363(00)00253-4
Abstract

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 TGFbeta(1) and PDGF-BB. Nebivolol concentration-dependently induced a moderate Apoptosis (10(-5) mol/l: 23%) 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.

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