Schmid, Evelyn and Neef, Stefan and Berlin, Christopher and Tomasovic, Angela and Kahlert, Katrin and Nordbeck, Peter and Deiss, Katharina and Denzinger, Sabrina and Herrmann, Sebastian and Wettwer, Erich and Weidendorfer, Markus and Becker, Daniel and Schaefer, Florian and Wagner, Nicole and Erguen, Sitleyman and Schmitt, Joachim P. and Katus, Hugo A. and Weidemann, Frank and Ravens, Ursula and Maack, Christoph and Hein, Lutz and Ertl, Georg and Mueller, Oliver J. and Maier, Lars S. and Lohse, Martin J. and Lorenz, Kristina (2015) Cardiac RKIP induces a beneficial beta-adrenoceptor-dependent positive inotropy. NATURE MEDICINE, 21 (11). pp. 1298-1306. ISSN 1078-8956, 1546-170X
Full text not available from this repository. (Request a copy)Abstract
In heart failure therapy, it is generally assumed that attempts to produce a long-term increase in cardiac contractile force are almost always accompanied by structural and functional damage. Here we show that modest overexpression of the Raf kinase inhibitor protein (RKIP), encoded by Pebp1 in mice, produces a well-tolerated, persistent increase in cardiac contractility that is mediated by the beta(1)-adrenoceptor (beta(1)AR). This result is unexpected, as beta(1)AR activation, a major driver of cardiac contractility, usually has long-term adverse effects. RKIP overexpression achieves this tolerance via simultaneous activation of the beta(2)AR subtype. Analogously, RKIP deficiency exaggerates pressure overload-induced cardiac failure. We find that RKIP expression is upregulated in mouse and human heart failure, indicative of an adaptive role for RKIP. Pebp1 gene transfer in a mouse model of heart failure has beneficial effects, suggesting a new therapeutic strategy for heart failure therapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN-KINASE-C; RYANODINE RECEPTOR PHOSPHORYLATION; HEART-FAILURE; BETA(2)-ADRENERGIC RECEPTOR; GENE-THERAPY; DILATED CARDIOMYOPATHY; RYR2 PHOSPHORYLATION; TARGETED DISRUPTION; FLIGHT RESPONSE; CONTRACTILITY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 May 2019 12:06 |
| Last Modified: | 07 May 2019 12:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4538 |
Actions (login required)
 |
View Item |
