betaARKct: a therapeutic approach for improved adrenergic signaling and function in heart disease

Brinks, Henriette; Koch, Walter J (2010). betaARKct: a therapeutic approach for improved adrenergic signaling and function in heart disease. Journal of cardiovascular translational research JCTR, 3(5), pp. 499-506. New York, N.Y.: Springer 10.1007/s12265-010-9206-6

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One of the most powerful regulators of cardiovascular function is catecholamine-stimulated adrenergic receptor (AR) signaling. The failing heart is characterized by desensitization and impaired beta-AR responsiveness as a result of upregulated G protein-coupled receptor kinase-2 (GRK2) present in injured myocardium. Deterioration of cardiac function is progressively enhanced by chronic adrenergic over-stimulation due to increased levels of circulating catecholamines. Increased GRK2 activity contributes to this pathological cycle of over-stimulation but lowered responsiveness. Over the past two decades the GRK2 inhibitory peptide betaARKct has been identified as a potential therapy that is able to break this vicious cycle of self-perpetuating deregulation of the beta-AR system and subsequent myocardial malfunction, thus halting development of cardiac failure. The betaARKct has been shown to interfere with GRK2 binding to the betagamma subunits of the heterotrimeric G protein, therefore inhibiting its recruitment to the plasma membrane that normally leads to phosphorylation and internalization of the receptor. In this article we summarize the current data on the therapeutic effects of betaARKct in cardiovascular disease and report on recent and ongoing studies that may pave the way for this peptide towards therapeutic application in heart failure and other states of cardiovascular disease.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiovascular Surgery

UniBE Contributor:

Most, Henriette

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1937-5387

Publisher:

Springer

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:13

Last Modified:

15 Dec 2014 15:41

Publisher DOI:

10.1007/s12265-010-9206-6

PubMed ID:

20623214

Web of Science ID:

000284694700010

URI:

https://boris.unibe.ch/id/eprint/2750 (FactScience: 205624)

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