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心力衰竭中心脏异常的磷酸化/去磷酸化和钙功能障碍。

Abnormal phosphorylation / dephosphorylation and Ca dysfunction in heart failure.

机构信息

Interventional Medical Center, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, Shandong Province, China.

Medical College, Qingdao University, Qingdao, China.

出版信息

Heart Fail Rev. 2024 Jul;29(4):751-768. doi: 10.1007/s10741-024-10395-w. Epub 2024 Mar 18.

Abstract

Heart failure (HF) can be caused by a variety of causes characterized by abnormal myocardial systole and diastole. Ca current through the L-type calcium channel (LTCC) on the membrane is the initial trigger signal for a cardiac cycle. Declined systole and diastole in HF are associated with dysfunction of myocardial Ca function. This disorder can be correlated with unbalanced levels of phosphorylation / dephosphorylation of LTCC, endoplasmic reticulum (ER), and myofilament. Kinase and phosphatase activity changes along with HF progress, resulting in phased changes in the degree of phosphorylation / dephosphorylation. It is important to realize the phosphorylation / dephosphorylation differences between a normal and a failing heart. This review focuses on phosphorylation / dephosphorylation changes in the progression of HF and summarizes the effects of phosphorylation / dephosphorylation of LTCC, ER function, and myofilament function in normal conditions and HF based on previous experiments and clinical research. Also, we summarize current therapeutic methods based on abnormal phosphorylation / dephosphorylation and clarify potential therapeutic directions.

摘要

心力衰竭(HF)可由多种原因引起,其特征为心肌收缩和舒张异常。细胞膜上的 L 型钙通道(LTCC)中的钙电流是心脏周期的初始触发信号。HF 中的收缩和舒张功能下降与心肌 Ca 功能障碍有关。这种紊乱与 LTCC、内质网(ER)和肌丝的磷酸化/去磷酸化平衡水平的改变有关。随着 HF 的进展,激酶和磷酸酶活性发生变化,导致磷酸化/去磷酸化程度的阶段性变化。重要的是要认识到正常心脏和衰竭心脏之间的磷酸化/去磷酸化差异。本综述重点关注 HF 进展过程中的磷酸化/去磷酸化变化,并根据以往的实验和临床研究总结了 LTCC、ER 功能和肌丝功能在正常和 HF 条件下的磷酸化/去磷酸化变化。此外,我们还总结了基于异常磷酸化/去磷酸化的当前治疗方法,并阐明了潜在的治疗方向。

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