Carvedilol inhibits platelet-derived growth factor-induced signal transduction in human cardiac fibroblasts

Journal of Cardiovascular Pharmacology
Ulrich LotzeHans R Figulla

Abstract

In the current study, first the platelet-derived growth factor (PDGF)-induced stimulation of the PDGF-beta receptor kinase in human cardiac fibroblasts was examined, and then the possibility of counterbalancing this signal transduction by carvedilol, a beta-blocker with alpha1-blocking properties, was investigated. Human cardiac fibroblasts were cultured from myocardial biopsy samples taken from patients with idiopathic dilated cardiomyopathy. The stimulation of the PDGF-beta receptor kinase by recombinant human PDGF (BB) in the cells and the inhibitory effect of carvedilol (1, 5, 10, and 20 microM) were investigated by analyzing PDGF-induced PDGF receptor tyrosine phosphorylation using Western blotting and by measuring DNA synthesis with a colorimetric assay. In human cardiac fibroblasts, the PDGF receptor kinase could be stimulated with PDGF (100 ng/ml) and inhibited with carvedilol (5 microM). In addition, carvedilol at a concentration of 5 microM significantly decreased DNA synthesis by approximately 50%. The inhibition of PDGF-stimulated mitogenesis by carvedilol at concentrations of 10 and 20 microM was 64 or 75%, respectively. Other beta-adrenoceptor antagonists such as propranolol (10 microM) and metoprolol (10 microM) ...Continue Reading

References

Jul 11, 1992·Journal of the American College of Cardiology·K T WeberC V Leier
Jun 1, 1992·Trends in Biochemical Sciences·S L Pelech, J S Sanghera
Jan 1, 1992·Journal of Cardiovascular Pharmacology·H J Why, P J Richardson
Dec 1, 1990·Circulation Research·C G BrillaK T Weber
Feb 1, 1993·Journal of Cardiovascular Pharmacology·C P SungE H Ohlstein
Mar 27, 1995·Annals of the New York Academy of Sciences·R P ButtJ E Bishop
Jul 1, 1994·Journal of Molecular and Cellular Cardiology·C G BrillaK T Weber
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·E H OhlsteinG Z Feuerstein
Jul 1, 1993·Physiological Reviews·V J Cristofalo, R J Pignolo
Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·G PagèsJ Pouysségur
Jul 18, 2000·Journal of the American College of Cardiology·S WeiJ E Sanderson
Jun 2, 2001·The New England Journal of Medicine·M PackerUNKNOWN Carvedilol Prospective Randomized Cumulative Survival Study Group

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