Altered Beta-adrenergic Receptor Gene Regulation and Signaling in Chronic Heart Failure

doi:10.1006/jmcc.2001.1358

Journal of Molecular and Cellular Cardiology

Volume 33, Issue 5, May 2001, Pages 887-905

https://doi.org/10.1006/jmcc.2001.1358 Get rights and content

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 (β -ARs) are critical regulators of cardiac function in both normal and pathophysiological states. Under normal conditions, β -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 β -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 β -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 β₁- v β₂-AR signaling pathways. Highlighting these differences is recent evidence that over-stimulation of theβ₁ -AR pathway in cardiac myocytes appears to be pro-apoptotic, whereas stimulation of theβ₂ -AR pathway may be anti-apoptotic. Overview of β -AR gene regulation, transgenic models ofβ -AR overexpression, and β -AR polymorphisms as they relate to heart failure progression are also discussed.

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^☆: Please address all correspondence to: Dr J. David Port, University of Colorado HSC, Division of Cardiology, B139, 4200 East Ninth Ave, Denver, CO 80262, USA. E-mail: [email protected]

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Regular ArticleAltered Beta-adrenergic Receptor Gene Regulation and Signaling in Chronic Heart Failure☆

Abstract

Am J Cardiol

J Mol Cell Cardiol

J Mol Cell Cardiol

J Biol Chem

J Biol Chem

J Mol Cell Cardiol

J Mol Cell Cardiol

J Mol Cell Cardiol

Am J Cardiol

Eur J Pharmacol

Trends Cell Biol

Curr Biol

J Biol Chem

Neuron

J Biol Chem

J Biol Chem

J Biol Chem

Cell

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

J Mol Cell Cardiol

Beta-adrenergic pathways in non-failing and failing human ventricular myocardium

Circulation

Adrenergic effects on the biology of the adult mammalian cardiocyte

Circulation

Changes in myocardial and vascular receptors in heart failure

J Am Coll Cardiol

Acute effects of beta 1-selective and nonselective beta-adrenergic receptor blockade on cardiac sympathetic activity in congestive heart failure

Circulation

Observations on the intracoronary administration of milrinone and dobutamine to patients with congestive heart failure

Am J Cardiol

Interactions between phospholamban and b-adrenergic drive may lead to cardiomyopathy and early mortality

Circulation

Effects of pressure overload, left ventricular hypertrophy on beta-adrenergic receptors, and responsiveness to catecholamines

J Clin Invest

Uber die Wirkung intravenoser adrenalin-injektion auf das Gefafssytem und ihre Beziehung zur Arteriosklerose

Beitrage zur Pathologischen Anatomie

Cellular and ventricular contractile dysfunction in experimental canine mitral regurgitation

Circ Res

Physiological and molecular correlates of age-related changes in the human beta-adrenergic receptor system

Fed Proc

Basal and isoprenaline-stimulated cAMP content in failing versus nonfailing human cardiac preparations

J Cardiovasc Pharmacol

Why do patients with congestive heart failure tolerate the initiation of beta-blocker therapy?

Circulation

Regulatory role of phospholamban in the efficiency of cardiac sarcoplasmic reticulum Ca(2+) transport

Biochemistry

Cardiac Gsalpha overexpression enhances L-type calcium channels through an adenylyl cyclase independent pathway

Proc Natl Acad Sci USA

Rapid β -adrenergic modulation of cardiac calcium channel currents by a fast G protein pathway

Science

Beta-adrenergic receptor blockade in chronic heart failure

Circulation

Medical therapy can improve the biological properties of the chronically failing heart. A new era in the treatment of heart failure

Circulation

Development of the concept of alpha and beta adrenotropic receptors

Ann N Y Acad Sci

Functional significance of presynaptic alpha-adrenergic receptors in failing and nonfailing human left ventricle

Circulation

Alpha 2C-adrenoceptor-modulated release of noradrenaline in human right atrium

Br J Pharmacol

The negative inotropic effect of beta3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle

J Clin Invest

Functional beta3-adrenoceptor in the human heart

J Clin Invest

Action potential shortening through the putative beta4-adrenoceptor in ferret ventricle: comparison with beta1- and beta2-adrenoceptor-mediated effects

Br J Pharmacol

[3H]alprenolol binding Proc Natl Acad Sci USA

Regular Article
Altered Beta-adrenergic Receptor Gene Regulation and Signaling in Chronic Heart Failure☆