| First Author | Schmid E | Year | 2015 |
| Journal | Nat Med | Volume | 21 |
| Issue | 11 | Pages | 1298-306 |
| PubMed ID | 26479924 | Mgi Jnum | J:228975 |
| Mgi Id | MGI:5749914 | Doi | 10.1038/nm.3972 |
| Citation | Schmid E, et al. (2015) Cardiac RKIP induces a beneficial beta-adrenoceptor-dependent positive inotropy. Nat Med 21(11):1298-306 |
| abstractText | 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 beta1-adrenoceptor (beta1AR). This result is unexpected, as beta1AR activation, a major driver of cardiac contractility, usually has long-term adverse effects. RKIP overexpression achieves this tolerance via simultaneous activation of the beta2AR 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. |
