Akt1 is required for physiological cardiac growth
Akt1 is required for physiological cardiac growth
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DOI：
10.1161/circulationaha.105.595231
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发表时间：
2006-05-02
期刊：
影响因子：
37.8
通讯作者：
Muslin, AJ
中科院分区：
文献类型：
--
作者：
DeBosch, B;Treskov, I;Muslin, AJ
背景-出生后心脏的生长主要涉及非增殖性心肌细胞的增大.心脏肥大以“生理”形式存在，其是对长期运动训练的适应性反应，并且作为“病理”形式存在，其通常是对刺激性刺激（例如高血压和主动脉瓣狭窄）的适应不良反应。一个信号级联，包括蛋白激酶Akt调节许多细胞类型的生长和生存，但Akt 1在任何形式的心脏肥大的确切作用是unknowed.Methods和结果-为了评估Akt 1在生理心脏生长的作用，Akt 1（-/-）成年小鼠心肌细胞（AMCMs）与IGF-1治疗，和Akt 1（-/-）小鼠进行运动训练。akt 1（-/-）AMCM对胰岛素样生长因子-1刺激的蛋白质合成具有抗性。发现akt 1（-/-）小鼠对游泳训练诱导的心脏肥大有抵抗力。为了评估Akt在病理性心脏生长中的作用，用内皮素-1处理akt 1（-/-）AMCM，并通过横向主动脉缩窄使akt 1（-/-）小鼠经受压力超负荷。令人惊讶的是，akt 1（-/-）AMCM敏感内皮素-1诱导的蛋白质合成，和akt 1（-/-）小鼠开发的心脏肥大的加剧形式，在响应于横向主动脉constrictions.Conclusions -这些结果建立Akt 1作为一个关键的调节开关，促进生理性心脏肥大，同时拮抗病理性肥大。
Background - Postnatal growth of the heart chiefly involves nonproliferative cardiomyocyte enlargement. Cardiac hypertrophy exists in a "physiological" form that is an adaptive response to long-term exercise training and as a "pathological" form that often is a maladaptive response to provocative stimuli such as hypertension and aortic valvular stenosis. A signaling cascade that includes the protein kinase Akt regulates the growth and survival of many cell types, but the precise role of Akt1 in either form of cardiac hypertrophy is unknown.Methods and Results - To evaluate the role of Akt1 in physiological cardiac growth, akt1(-/-) adult murine cardiac myocytes (AMCMs) were treated with IGF-1, and akt1(-/-) mice were subjected to exercise training. akt1(-/-) AMCMs were resistant to insulin-like growth factor-1-stimulated protein synthesis. The akt1(-/-) mice were found to be resistant to swimming training - induced cardiac hypertrophy. To evaluate the role of Akt in pathological cardiac growth, akt1(-/-) AMCMs were treated with endothelin-1, and akt1(-/-) mice were subjected to pressure overload by transverse aortic constriction. Surprisingly, akt1(-/-) AMCMs were sensitized to endothelin-1-induced protein synthesis, and akt1(-/-) mice developed an exacerbated form of cardiac hypertrophy in response to transverse aortic constriction.Conclusions - These results establish Akt1 as a pivotal regulatory switch that promotes physiological cardiac hypertrophy while antagonizing pathological hypertrophy.