磷酸化修饰在病理性心肌肥大中的作用

The role of phosphorylation in pathological myocardial hypertrophy

心肌肥大与高水平神经-体液因子、血流动力学超负荷、心肌细胞的损伤有关,如果病因持续存在或未及时消除,最终将演变为慢性心力衰竭。在病理性心肌肥大的发生发展过程中,磷酸化修饰可以精确地调节和改善丝裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)、钙调磷酸酶(calcineurin,CAN)、钙调素依赖性蛋白酶Ⅱ(calmodulin dependent protein kinaseⅡ,CaMKⅡ)、蛋白激酶B(protein kinase B,PKB/AKT)、单磷酸腺苷依赖的蛋白激酶(adenosine 5-monophosphate-activated protein kinase,AMPK)、核因子κB(nuclear factor kappa-B,NF-κB)信号通路以及细胞自噬的稳定性和活性。本文分别总结了磷酸化修饰在病理性心肌肥大中的作用机制以及治疗或预防心肌肥大的潜在靶点,探索病理性心肌肥大中基于质谱的磷酸化蛋白质组学进展,为未来心脏病学转化研究提供参考。

Cardiac hypertrophy is associated with high levels of neurohumoral factors,hemodynamic overload,and myocardial cell injury.If the causative factors persist or are not promptly eliminated,it eventually progresses to chronic heart failure.During the occurrence and development of pathological cardiac hypertrophy,phosphorylation modification can precisely regulate and improve the signaling pathways of mitogen activated protein kinase(MAPK),calcineurin(CAN),calmodulin dependent protein kinase II(CaMKⅡ),protein kinase B(PKB/AKT),adenosine 5-monophosphate-activated protein kinase(AMPK),nuclear factor kappa-B(NF-κB),as well as the stability and activity of cellular autophagy.This paper summarizes the mechanisms of phosphorylation modification in pathological cardiac hypertrophy and explores potential targets for the treatment or prevention of myocardial hypertrophy,through the advancement of mass spectrometry-based phosphoproteomics in pathological cardiac hypertrophy.It provides reference for future translational research in cardiology.