A potential role for integrin signaling in mechanoelectrical feedback.
A potential role for integrin signaling in mechanoelectrical feedback.
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DOI：
10.1016/j.pbiomolbio.2012.07.002
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发表时间：
2012-10
影响因子：
3.8
通讯作者：
Parker KK
中科院分区：
文献类型：
--
作者：
Dabiri BE;Lee H;Parker KK
某些形式的心脏病涉及改变其血流动力学负荷条件的心肌的总体形态学变化。这些变化可最终导致细胞外基质（ECM）蛋白（如胶原蛋白和纤连蛋白）沉积增加，其共同作用以病理性地改变心肌的整体组织力学。除了改变心脏的机械特性之外，这种适应不良的重构引起心肌电导率和同步性的变化，因为组织的机械特性与其电特性密切相关。这种现象被称为机电耦合（MEC），可使受心脏病影响的个体易患心脏性猝死（SCD）。MEC的潜在机制已被归因于各种过程，包括牵张激活通道的作用和肌钙蛋白C-Ca 2+结合亲和力的变化。然而，心肌梗死后或由于先天性肌病引起的心脏变化也伴随着心肌细胞的各种分子组分表达的变化，包括整联蛋白的机械敏感性家族。作为跨膜蛋白，整联蛋白机械地偶联ECM与细胞内细胞骨架，并且已经涉及介导各种细胞类型（包括神经元和平滑肌）中的离子稳态。鉴于心脏病背景下整合素表达改变的证据，加上相关的心律失常风险增加，我们认为在这篇综述中，整合素信号有助于MEC。鉴于与心律失常和SCD相关的显著死亡率，有必要仔细检查所有可归咎的机制，包括整合素介导的MEC。
Certain forms of heart disease involve gross morphological changes to the myocardium that alter its hemodynamic loading conditions. These changes can ultimately lead to the increased deposition of extracellular matrix (ECM) proteins, such as collagen and fibronectin, which together work to pathologically alter the myocardium’s bulk tissue mechanics. In addition to changing the mechanical properties of the heart, this maladaptive remodeling gives rise to changes in myocardium electrical conductivity and synchrony since the tissue’s mechanical properties are intimately tied to its electrical characteristics. This phenomenon, called mechanoelectrical coupling (MEC), can render individuals affected by heart disease arrhythmogenic and susceptible to sudden cardiac death (SCD). The underlying mechanisms of MEC have been attributed to various processes, including the action of stretch activated channels and changes in troponin C-Ca2+ binding affinity. However, changes in the heart post infarction or due to congenital myopathies are also accompanied by shifts in the expression of various molecular components of cardiomyocytes, including the mechanosensitive family of integrin proteins. As transmembrane proteins, integrins mechanically couple the ECM with the intracellular cytoskeleton and have been implicated in mediating ion homeostasis in various cell types, including neurons and smooth muscle. Given evidence of altered integrin expression in the setting of heart disease coupled with the associated increased risk for arrhythmia, we argue in this review that integrin signaling contributes to MEC. In light of the significant mortality associated with arrhythmia and SCD, close examination of all culpable mechanisms, including integrin-mediated MEC, is necessary.