Role of Protein Quality Control in Cardiac Remodeling

在血流动力学负荷增加的情况下，心肌细胞发生肥大，以适应增加的工作负荷，减少壁应力。但是，心肌肥厚的长期存在是心脏病发病率和死亡率的独立危险因素。在这里，我们研究了肌肉萎缩F-box(MAFbx/Avergin-1)，一种E3泛素连接酶，在调节心肌肥厚和压力超负荷反应中的作用。与野生型(WT)小鼠相比，MAFbx基因敲除(KO)小鼠的横动脉缩窄(TAC)和β肾上腺素能引起的心肌肥厚和肺充血增加明显较小。MAFbx的下调抑制心肌肥厚，部分是通过稳定I.B和失活核因子-1。B.抑制MAFbx可减轻病理性肥厚，从而保护心脏免于进展为心力衰竭。

Under condition of increased hemodynamic load, cardiomyocytes undergo hypertrophy to adapt to increased work load and reduce wall stress. But, the prolonged existence of cardiac hypertrophy is an independent risk factor for cardiac morbidity and mortality. Here, we investigated the role of muscle atrophy F-box(MAFbx/atrogin-1), an E3 ubiquitin ligase, in regulating cardiac hypertrophy and function in response to pressure overload. Transverse aortic constriction(TAC)-andβ.-adrenergic-induced increases in cardiac hypertrophy and lung congestion were significantly smaller in MAFbx knockout(KO) than in wild-type(WT) mice. Downregulation of MAFbx inhibits cardiac hypertrophy in part through stabilization of I. B and inactivation of nuclea factor-. B. Inhibition of MAFbx attenuates pathological hypertrophy, thereby protecting the heart from progression into heart failure.