机械刺激诱导心肌细胞肥大的分子机制

Mechanism of Mechanical Stress Inducing Cardiomyocyte Hypertrophy

机械负荷过度将导致病理性心肌肥大并严重危害人类健康。机械刺激作用于心肌细胞后,可通过细胞表面的机械感受器(如整合素)或分泌细胞因子(血管紧张素Ⅱ及内皮素等),激活一系列信号通路,主要的有丝裂原激活蛋白激酶通路、詹纳斯激酶/信号转导蛋白转录激活因子通路及由钙离子介导的信号通路。心肌细胞将机械信号转化为化学信号,调节肥大相关基因的表达,致使心肌细胞发生肥大。

Pressure overload plays a crucial role in pathological cardiac hypertrophy. Mechanical stress stimulates a series of hypertrophic signal transduction pathways via the mechanosensors on cardiomyocytes surface as integrin or inducing the release of cytokines as Angiotensin Ⅱ and endothelin. The signal transduc- tion pathways mainly include mitogenic-activatcd protein kinase signal way, Janus kinase/signal transducers and activator of transcription signal way and ealcineurin signal way. Cardiomyocytes convert mechanical signal into chemical signal, adjusting the hypertrophy related gene expression, resulting in cardiomyocyte hypertrophy.