Myocardial G protein-coupled receptor kinases: Implications for heart failure therapy

G. Iaccarino, R. J. Lefkowitz, W. J. Koch

Research output: Contribution to journalArticle

Abstract

The β-adrenergic signaling cascade is an important regulator of myocardial function. Significant alterations of this pathway are associated with several cardiovascular diseases, including congestive heart failure (CHF). Included in these alterations is increased activity and expression of G protein-coupled receptor kinases (GRKs), such as the β-adrenergic receptor kinase (βARK1), which phosphorylate and desensitize β-adrenergic receptors (βARs). A body of evidence is accumulating that suggests that GRKs, in particular βARK1, are critical determinants of cardiac function under normal conditions and in disease states. Transgenic mice with myocardial-targeted alterations of GRK activity have shown profound changes in the in vivo functional performance of the heart. Included in these studies is the compelling finding that inhibition of βARK1 activity or expression significantly enhances cardiac function and potentiates βAR signaling in failing cardiomyocytes. This article summarizes the advances made in the study of βARK1 in the heart and addresses its potential as a novel therapeutic target for CHF.

Original languageEnglish
Pages (from-to)399-405
Number of pages7
JournalProceedings of the Association of American Physicians
Volume111
Issue number5
Publication statusPublished - 1999

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Keywords

  • β- blockers
  • β-adrenergic receptor kinase
  • Adrenergic signaling
  • Desensitization
  • Sympathetic nervous system
  • Transgenic mice

ASJC Scopus subject areas

  • Medicine(all)

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