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J Physiol. 2017 Jun 15;595(12):4073-4087. doi: 10.1113/JP274064. Epub 2017 May 23.

Raf kinase inhibitor protein: lessons of a better way for β-adrenergic receptor activation in the heart.

Author information

1
Comprehensive Heart Failure Center, University of Würzburg, Versbacher Straße 9, 97078, Würzburg, Germany.
2
West German Heart and Vascular Center Essen, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany.
3
Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Bunsen-Kirchhoff-Straße 11, 44139, Dortmund, Germany.
4
Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Straße 9, 97078, Würzburg, Germany.
5
Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
6
Institute of Pharmacology and Clinical Pharmacology, Düsseldorf University Hospital, Universtitätsstraße 1, 40225, Düsseldorf, Germany.
7
Cardiovascular Research Institute Düsseldorf (CARID), Heinrich-Heine-University, Universtitätsstraße 1, 40225, Düsseldorf, Germany.

Abstract

Stimulation of β-adrenergic receptors (βARs) provides the most efficient physiological mechanism to enhance contraction and relaxation of the heart. Activation of βARs allows rapid enhancement of myocardial function in order to fuel the muscles for running and fighting in a fight-or-flight response. Likewise, βARs become activated during cardiovascular disease in an attempt to counteract the restrictions of cardiac output. However, long-term stimulation of βARs increases the likelihood of cardiac arrhythmias, adverse ventricular remodelling, decline of cardiac performance and premature death, thereby limiting the use of βAR agonists in the treatment of heart failure. Recently the endogenous Raf kinase inhibitor protein (RKIP) was found to activate βAR signalling of the heart without adverse effects. This review will summarize the current knowledge on RKIP-driven compared to receptor-mediated signalling in cardiomyocytes. Emphasis is given to the differential effects of RKIP on β1 - and β2 -ARs and their downstream targets, the regulation of myocyte calcium cycling and myofilament activity.

KEYWORDS:

RKIP; beta-adrenergic receptors; heart failure

PMID:
28444807
PMCID:
PMC5471367
DOI:
10.1113/JP274064
[Indexed for MEDLINE]
Free PMC Article

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