Altered myocardial calcium cycling and energetics in heart failure--a rational approach for disease treatment.

Altered myocardial calcium cycling and energetics in heart failure--a rational approach for disease treatment.
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DOI:
10.1016/j.cmet.2015.01.005
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发表时间:
2015-02-03
期刊:
影响因子:
29
通讯作者:
Hajjar RJ
Hajjar RJ
中科院分区:
生物学1区
文献类型:
--
作者:
Gorski PA;Ceholski DK;Hajjar RJ

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心肌细胞的功能取决于钙进出细胞的协调运动以及ATP向能量利用酶的适当递送。钙处理蛋白的缺陷和能量代谢异常是心力衰竭的特征。最近的发现已经导致靶向钙转运或钙结合蛋白的基于基因的疗法,例如心脏肌浆网钙ATP酶(SERCA 2a),从而导致钙稳态和兴奋-收缩偶联的改善。在这里,我们审查受损的钙循环和能量在心力衰竭,评估他们的作用,从相互排斥和相互依存的观点,并讨论治疗,可能会改善失败的心肌。
Cardiomyocyte function depends on coordinated movements of calcium into and out of the cell and the proper delivery of ATP to energy-utilizing enzymes. Defects in calcium-handling proteins and abnormal energy metabolism are features of heart failure. Recent discoveries have led to gene-based therapies targeting calcium-transporting or -binding proteins, such as the cardiac sarco(endo)plasmic reticulum calcium ATPase (SERCA2a), leading to improvements in calcium homeostasis and excitation-contraction coupling. Here we review impaired calcium cycling and energetics in heart failure, assessing their roles from both a mutually exclusive and interdependent viewpoint, and discuss therapies that may improve the failing myocardium.
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