Title |
Cardiac RKIP induces a beneficial β-adrenoceptor–dependent positive inotropy
|
---|---|
Published in |
Nature Medicine, October 2015
|
DOI | 10.1038/nm.3972 |
Pubmed ID | |
Authors |
Evelyn Schmid, Stefan Neef, Christopher Berlin, Angela Tomasovic, Katrin Kahlert, Peter Nordbeck, Katharina Deiss, Sabrina Denzinger, Sebastian Herrmann, Erich Wettwer, Markus Weidendorfer, Daniel Becker, Florian Schäfer, Nicole Wagner, Süleyman Ergün, Joachim P Schmitt, Hugo A Katus, Frank Weidemann, Ursula Ravens, Christoph Maack, Lutz Hein, Georg Ertl, Oliver J Müller, Lars S Maier, Martin J Lohse, Kristina Lorenz |
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 β1-adrenoceptor (β1AR). This result is unexpected, as β1AR activation, a major driver of cardiac contractility, usually has long-term adverse effects. RKIP overexpression achieves this tolerance via simultaneous activation of the β2AR 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. |
X Demographics
As of 1 July 2024, you may notice a temporary increase in the numbers of X profiles with Unknown location. Click here to learn more.
Geographical breakdown
Country | Count | As % |
---|---|---|
Italy | 3 | 25% |
France | 1 | 8% |
United States | 1 | 8% |
United Kingdom | 1 | 8% |
Spain | 1 | 8% |
Ecuador | 1 | 8% |
Unknown | 4 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 8 | 67% |
Scientists | 2 | 17% |
Practitioners (doctors, other healthcare professionals) | 1 | 8% |
Science communicators (journalists, bloggers, editors) | 1 | 8% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Germany | 1 | 1% |
Unknown | 67 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 16 | 24% |
Researcher | 9 | 13% |
Student > Doctoral Student | 8 | 12% |
Student > Master | 7 | 10% |
Student > Bachelor | 5 | 7% |
Other | 10 | 15% |
Unknown | 13 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 16 | 24% |
Medicine and Dentistry | 13 | 19% |
Agricultural and Biological Sciences | 13 | 19% |
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 9% |
Nursing and Health Professions | 3 | 4% |
Other | 2 | 3% |
Unknown | 15 | 22% |