Cardiotrophin 1 Stimulates Beneficial Myogenic and Vascular Remodeling of the Heart

Overview

Journal Cell Res

Specialty Cell Biology

Date 2017 Aug 9

PMID 28785017

Citations 21

Authors

Mohammad Abdul-Ghani

Colin Suen

Baohua Jiang

Yupu Deng

Jonathan J Weldrick

Charis Putinski

Steve Brunette

Pasan Fernando

Tom T Lee

Peter Flynn

Frans H H Leenen

Patrick G Burgon

Duncan J Stewart

Lynn A Megeney

Affiliations

Soon will be listed here.

Abstract

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.

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