Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart

被引：35

作者：

Abdul-Ghani, Mohammad ^{[1
,2
]}

Suen, Colin ^{[1
,2
]}

Jiang, Baohua ^{[1
]}

Deng, Yupu ^{[1
]}

Weldrick, Jonathan J. ^{[2
,3
]}

Putinski, Charis ^{[1
,2
]}

Brunette, Steve ^{[1
]}

Fernando, Pasan ^{[1
,4
]}

Lee, Tom T. ^{[5
]}

Flynn, Peter ^{[5
]}

Leenen, Frans H. H. ^{[2
,3
,6
]}

Burgon, Patrick G. ^{[2
,3
,6
]}

Stewart, Duncan J. ^{[1
,2
,6
]}

Megeney, Lynn A. ^{[1
,2
,6
]}

机构：

[1] Ottawa Hosp, Res Inst, Regenerat Med Program, Sprott Ctr Stem Cell Res, Ottawa, ON K1H 8L6, Canada

[2] Univ Ottawa, Dept Cellular & Mol Med, Fac Med, Ottawa, ON K1H 8M5, Canada

[3] Univ Ottawa, Heart Inst, Ottawa, ON K1Y 4W7, Canada

[4] Carleton Univ, Dept Biol, Ottawa, ON K1S 5B6, Canada

[5] Fate Therapeut Inc, 3535 Gen Atom Court Suite 200, San Diego, CA 92121 USA

[6] Univ Ottawa, Dept Med Cardiol, Fac Med, Ottawa, ON K1H 8M5, Canada

来源：

CELL RESEARCH | 2017年 / 27卷 / 10期

基金：

加拿大健康研究院;

关键词：

cardiotrophin; 1; cardiac; hypertrophy; right heart failure; physiologic; reversible; caspase; PULMONARY ARTERIAL-HYPERTENSION; PATHOLOGICAL CARDIAC-HYPERTROPHY; SIGNAL TRANSDUCER; CELL-DEATH; CARDIOMYOCYTE HYPERTROPHY; VENTRICULAR HYPERTROPHY; MECHANICAL-PROPERTIES; MOLECULAR-MECHANISMS; CASPASE ACTIVATION; TRANSGENIC MICE;

D O I：

10.1038/cr.2017.87

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1195 / 1215

页数：21

共 70 条

[11] The benefits of endurance training in cardiomyocyte function in hypertensive rats are reversed within four weeks of detraining [J].