Volume 27, No 10, Oct 2017
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 27 Issue 10, October 2017: 1195-1215 | Open Access
ORIGINAL ARTICLES
Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart
Mohammad Abdul-Ghani1,2,*, Colin Suen1,2,*, Baohua Jiang1, Yupu Deng1, Jonathan J Weldrick2,3, Charis Putinski1,2, Steve Brunette1, Pasan Fernando1,4, Tom T Lee5, Peter Flynn5, Frans H H Leenen2,6,3, Patrick G Burgon2,6,3, Duncan J Stewart1,2,6 and Lynn A Megeney1,2,6
1Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, Ontario K1H 8L6, Canada
2Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
3University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada
4Department of Biology, Carleton University, Ottawa, Ontario K1S 5B6, Canada
5Fate Therapeutics Inc., 3535 General Atomics Court Suite 200, San Diego, CA 92121, USA
6Department of Medicine (Cardiology), Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
Correspondence: Lynn A Megeney, E-mail: lmegeney@ohri.ca; Duncan J Stewart,(djstewart@ohri.ca)
The post-natal heart adapts to stress and overload through hypertrophic growth, a process that may be pathologic or beneficial (physiologic hypertrophy). Physiologic hypertrophy improves cardiac performance in both healthy and diseased individuals, yet the mechanisms that propagate this favorable adaptation remain poorly defined. We identify the cytokine cardiotrophin 1 (CT1) as a factor capable of recapitulating the key features of physiologic growth of the heart including transient and reversible hypertrophy of the myocardium, and stimulation of cardiomyocyte-derived angiogenic signals leading to increased vascularity. The capacity of CT1 to induce physiologic hypertrophy originates from a CK2-mediated restraining of caspase activation, preventing the transition to unrestrained pathologic growth. Exogenous CT1 protein delivery attenuated pathology and restored contractile function in a severe model of right heart failure, suggesting a novel treatment option for this intractable cardiac disease.
10.1038/cr.2017.87
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