Nass Robert D, Aiba Takeshi, Tomaselli Gordon F, Akar Fadi G
Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
Nat Clin Pract Cardiovasc Med. 2008 Apr;5(4):196-207. doi: 10.1038/ncpcardio1130. Epub 2008 Mar 4.
In an attempt to compensate for compromised hemodynamics in heart failure, neurohumoral mechanisms are activated that trigger fundamental changes in gene expression and in protein processing, trafficking and post-translational regulation, resulting in myocyte hypertrophy. Unfortunately, over time these changes become maladaptive, predisposing to myocyte loss, chamber dilatation, interstitial hyperplasia and intercellular uncoupling. Intrinsic and peripheral responses to mechanical dysfunction alter the expression and function of key ion channels and calcium-handling proteins, thereby remodeling the cellular action potential and the intracellular calcium transient. This electrophysiological remodeling renders the heart more vulnerable to ventricular arrhythmias that underlie sudden cardiac death. In this Review, we consider key ventricular ionic changes that are associated with heart failure, with the intention of identifying molecular targets for antiarrhythmic therapy.
为了代偿心力衰竭时受损的血流动力学，神经体液机制被激活，从而引发基因表达以及蛋白质加工、运输和翻译后调控的根本性变化，导致心肌细胞肥大。遗憾的是，随着时间的推移，这些变化会变得适应不良，易导致心肌细胞丢失、心腔扩张、间质增生和细胞间去耦联。对机械功能障碍的内在和外周反应会改变关键离子通道和钙处理蛋白的表达与功能，从而重塑细胞动作电位和细胞内钙瞬变。这种电生理重塑使心脏更容易发生作为心源性猝死基础的室性心律失常。在本综述中，我们探讨与心力衰竭相关的关键心室离子变化，旨在确定抗心律失常治疗的分子靶点。
