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.

中文翻译：

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心肌营养素1刺激心脏的有益的肌原性和血管重塑。

产后心脏通过肥大性生长适应压力和超负荷，该过程可能是病理性的或有益的（生理性肥大）。生理性肥大可改善健康人和患病个体的心脏功能，但传播这种有利适应性的机制仍然不清楚。我们确定细胞因子心肌营养素1（CT1）作为能够概括心脏的生理生长的关键特征的因素，包括短暂和可逆的心肌肥大，以及刺激心肌细胞衍生的血管生成信号，从而导致血管增多。CT1诱导生理性肥大的能力源于CK2介导的对caspase激活的抑制，从而阻止了向不受约束的病理性生长的过渡。