Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Number 314 Anshanxi Road, Nankai District, Tianjin, 300193, People's Republic of China.
State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People's Republic of China.
Heart Fail Rev. 2020 May;25(3):523-535. doi: 10.1007/s10741-019-09873-3.
Calcium ion (Ca) cycle plays a crucial role in the contraction and relaxation of cardiomyocytes. The sarcoplasmic reticulum (SR) acts as an organelle for storing Ca, which mediated the release and re-uptake of Ca during contraction and relaxation. Disorders of SR function lead to the dysfunction of Ca cycle and myocardial cell function. The sarcoplasmic/endoplasmic reticulum Ca ATPase 2a (SERCA2a) acts as a subtype of SERCA expressed in the heart, which mediates the contraction of cardiomyocytes and Ca in the cytoplasm to re-enter into the SR. The rate of uptake of Ca by the SR determines the rate of myocardial relaxation. The regulation of SERCA2a activity controls the contractility and relaxation of the heart, affecting cardiac function. The expression and activity of SERCA2a are reduced in failing hearts. Gene therapy by increasing the expression of SERCA2a in the heart has been proven effective. In addition, SERCA2a is regulated by a variety of factors, including transmembrane micropeptides, protein kinases, and post-translational modifications (PTMs). In this review, we discuss the regulatory factors of SERCA2a and provide new insights into future treatments and the direction of heart failure research. In addition, gene therapy for SERCA2a has recently emerged as therapeutic option and hence will be discussed in this review.
钙离子（Ca）循环在心肌细胞的收缩和舒张中起着至关重要的作用。肌浆网（SR）作为储存 Ca 的细胞器，在收缩和舒张过程中介导 Ca 的释放和再摄取。SR 功能障碍会导致 Ca 循环和心肌细胞功能障碍。肌浆网/内质网 Ca ATP 酶 2a（SERCA2a）作为心脏中表达的 SERCA 的一种亚型，介导心肌细胞的收缩和细胞质中的 Ca 重新进入 SR。SR 对 Ca 的摄取速率决定了心肌舒张的速率。SERCA2a 活性的调节控制着心脏的收缩和舒张，影响心脏功能。衰竭心脏中 SERCA2a 的表达和活性降低。通过增加心脏中 SERCA2a 的表达进行基因治疗已被证明是有效的。此外，SERCA2a 的表达和活性受到多种因素的调节，包括跨膜微肽、蛋白激酶和翻译后修饰（PTMs）。在这篇综述中，我们讨论了 SERCA2a 的调节因子，并为未来的治疗方法和心力衰竭研究方向提供了新的见解。此外，SERCA2a 的基因治疗最近已成为一种治疗选择，因此将在本综述中进行讨论。
