| Effects of nebivolol on proliferation and apoptosis of human coronary artery smooth muscle and endothelial cells. | |
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MedLine Citation:
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PMID: 11164853 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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B R Brehm; S C Wolf; D Bertsch; M Klaussner; S Wesselborg; S Schüler; K Schulze-Osthoff |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Cardiovascular research Volume: 49 ISSN: 0008-6363 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2001 Feb |
Date Detail:
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Created Date: 2001-02-22 Completed Date: 2001-04-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 430-9 Citation Subset: IM |
Affiliation:
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Department of Cardiology, University of Tübingen, Otfried-Müllerstrasse 10, 72076, Tübingen, Germany. bernard_brehm@compuserve.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-Antagonists
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pharmacology* Apoptosis / drug effects* Benzopyrans / pharmacology* Bisoprolol / pharmacology Cell Culture Techniques Cell Division / drug effects Cells, Cultured Depression, Chemical Dose-Response Relationship, Drug Endothelin-1 / metabolism, secretion Endothelins / genetics Endothelium, Vascular / drug effects*, metabolism Ethanolamines / pharmacology* Gene Expression / drug effects Humans In Situ Hybridization Male Metoprolol / pharmacology Muscle, Smooth, Vascular / drug effects*, metabolism Nitric Oxide / metabolism Platelet-Derived Growth Factor / pharmacology Propranolol / pharmacology Protein Precursors / genetics RNA, Messenger / analysis Transforming Growth Factor beta / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Antagonists; 0/Benzopyrans; 0/Endothelin-1; 0/Endothelins; 0/Ethanolamines; 0/Platelet-Derived Growth Factor; 0/Protein Precursors; 0/RNA, Messenger; 0/Transforming Growth Factor beta; 0/platelet-derived growth factor A; 0/platelet-derived growth factor BB; 10102-43-9/Nitric Oxide; 37350-58-6/Metoprolol; 525-66-6/Propranolol; 66722-44-9/Bisoprolol; 99200-09-6/nebivolol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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