The cardiomyocyte plasma membrane, termed the sarcolemma, is fundamental for regulating a myriad of cellular processes. For example, the structural integrity of the cardiomyocyte sarcolemma is essential for mediating cardiac contraction by forming microdomains such as the t-tubular network, caveolae and the intercalated disc. Significantly, remodelling of these sarcolemma microdomains is a key feature in the development and progression of heart failure (HF). However, despite extensive characterisation of the associated molecular and ultrastructural events there is a lack of clarity surrounding the mechanisms driving adverse morphological rearrangements. The sarcolemma also provides protection, and is the cell’s first line of defence, against external stresses such as oxygen and nutrient deprivation, inflammation and oxidative stress with a loss of sarcolemma viability shown to be a key step in cell death via necrosis. Significantly, cumulative cell death is also a feature of HF, and is linked to disease progression and loss of cardiac function. Herein, we will review the link between structural and molecular remodelling of the sarcolemma associated with the progression of HF, specifically considering the evidence for: (i) Whether intrinsic, evolutionary conserved, plasma membrane injury-repair mechanisms are in operation in the heart, and (ii) if deficits in key ‘wound-healing’ proteins (annexins, dysferlin, EHD2 and MG53) may play a yet to be fully appreciated role in triggering sarcolemma microdomain remodelling and/or necrosis. Cardiomyocytes are terminally differentiated with very limited regenerative capability and therefore preserving cell viability and cardiac function is crucially important. This review presents a novel perspective on sarcolemma remodelling by considering whether targeting proteins that regulate sarcolemma injury-repair may hold promise for developing new strategies to attenuate HF progression.

中文翻译：

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心肌细胞损伤控制在心力衰竭和肌膜炎的作用。

被称为肌膜膜的心肌细胞质膜是调节众多细胞过程的基础。例如，心肌细胞肉瘤的结构完整性对于通过形成微结构域（例如T管网络，海绵体和插入的椎间盘）来介导心脏收缩至关重要。重要的是，这些肌膜微区的重塑是心力衰竭（HF）发生和发展的关键特征。然而，尽管对相关的分子和超微结构事件进行了广泛的表征，但是围绕驱动不良形态重排的机制仍缺乏清晰性。肌膜层还提供保护，并且是细胞的第一道防线，可以抵抗外界压力，例如氧气和营养物质的缺乏，炎症和氧化应激以及肌膜细胞活力的丧失是坏死导致细胞死亡的关键步骤。值得注意的是，累积细胞死亡也是HF的特征，与疾病进展和心脏功能丧失有关。在这里，我们将回顾与HF病程相关的肌膜结构和分子重塑之间的联系，特别是要考虑以下证据：（i）是否固有，进化保守，质膜损伤-修复机制在心脏中起作用，并且（ii）如果关键的“伤口愈合”蛋白（annexins，dysferlin，EHD2和MG53）缺乏，可能在触发肌膜微区重塑中起尚未被充分认识的作用和/或坏死。心肌细胞的终末分化能力非常有限，因此保持细胞活力和心脏功能至关重要。这篇综述通过考虑靶向调节肌膜损伤修复的靶蛋白是否可能为开发减弱HF进展的新策略提供希望，从而提出了肌膜重构的新观点。