Altered beta-adrenergic receptor gene regulation and signaling in chronic heart failure.
J Mol Cell Cardiol
; 33(5): 887-905, 2001 May.
Article
de En
| MEDLINE
| ID: mdl-11343413
ABSTRACT
J. D. Port and M. R. Bristow. Altered Beta-adrenergic Receptor Gene Regulation and Signaling in Chronic Heart Failure. Journal of Molecular and Cellular Cardiology (2001) 33, 887-905. Beta adrenergic receptors (beta -ARs) are critical regulators of cardiac function in both normal and pathophysiological states. Under normal conditions, beta -ARs and their signaling pathways modulate both the rate and force of myocardial contraction and relaxation, allowing individuals to respond appropriately to physiological stress or exercise. However, in chronic heart failure, sustained activation of the beta -AR signaling pathways can have overtly negative biological consequences. This notion is reinforced by the positive outcomes of a number of clinical trials demonstrating the usefulness of beta-blocker therapy in chronic congestive heart failure. During the last few years, significant progress has been made in understanding the molecular biological basis of beta -AR function, both at the biochemical and genetic levels. In this review, the biological basis of adrenergic signaling and how this changes in heart failure is discussed. Aspects of adrenergic receptor pharmacology relevant to heart failure are reviewed, including the recently emerging differences described for beta(1)- v beta(2)-AR signaling pathways. Highlighting these differences is recent evidence that over-stimulation of the beta(1)-AR pathway in cardiac myocytes appears to be pro-apoptotic, whereas stimulation of the beta(2)-AR pathway may be anti-apoptotic. Overview of beta -AR gene regulation, transgenic models of beta -AR overexpression, and beta -AR polymorphisms as they relate to heart failure progression are also discussed.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Transduction du signal
/
Régulation de l'expression des gènes
/
Récepteurs bêta-adrénergiques
/
Défaillance cardiaque
Limites:
Animals
/
Humans
Langue:
En
Journal:
J Mol Cell Cardiol
Année:
2001
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique