Interventional Medical Center, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, Shandong Province, China.
Medical College, Qingdao University, Qingdao, China.
Heart Fail Rev. 2024 Jul;29(4):751-768. doi: 10.1007/s10741-024-10395-w. Epub 2024 Mar 18.
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.
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。