Mechanotransduction in cardiac hypertrophy and failure.
Mechanotransduction in cardiac hypertrophy and failure.
复制标题
心脏肥大和衰竭的机械转导。
DOI：
10.1161/circresaha.116.304937
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发表时间：
2015-04-10
影响因子：
20.1
通讯作者：
Sheikh F
中科院分区：
文献类型：
--
作者：
Lyon RC;Zanella F;Omens JH;Sheikh F
心肌细胞具有通过称为机械转导的过程感知和响应机械负荷的内在能力。在心脏中，这一过程涉及机械刺激转化为生物化学事件，引起心肌结构和功能的变化。机械传导及其下游效应最初作为适应性反应起作用，在适应初始负荷期间作为补偿机制。然而，在长期和异常负荷条件下，重塑过程可能变得不适应，导致生理功能改变和病理性心脏肥大和心力衰竭的发展。虽然机械转导的机制还远未完全阐明，人类和小鼠的遗传学研究已经强调了心肌细胞中的各种细胞骨架和肌膜结构作为负荷换能器的可能候选者，基于它们与疾病发病机制中重要的信号分子和结构成分的联系。在这篇综述中，我们总结了最近的发展，已经发现特定的蛋白质复合物连接到机械转导和机械传递内（1）肌节，（2）闰盘，（3）在肌膜。作为机械转换器的蛋白质结构是驱动生理和病理性心脏肥大和重塑以及向心力衰竭转变的过程中的第一步，并且可以更好地了解驱动基于机械转换的疾病的机制。
Cardiac muscle cells have an intrinsic ability to sense and respond to mechanical load through a process known as mechanotransduction. In the heart, this process involves the conversion of mechanical stimuli into biochemical events that induce changes in myocardial structure and function. Mechanotransduction and its downstream effects function initially as adaptive responses that serve as compensatory mechanisms during adaptation to the initial load. However, under prolonged and abnormal loading conditions, the remodeling processes can become maladaptive, leading to altered physiological function and the development of pathological cardiac hypertrophy and heart failure. Although the mechanisms underlying mechanotransduction are far from being fully elucidated, human and mouse genetic studies have highlighted various cytoskeletal and sarcolemmal structures in cardiac myocytes as the likely candidates for load transducers, based on their link to signaling molecules and architectural components important in disease pathogenesis. In this review, we summarize recent developments that have uncovered specific protein complexes linked to mechanotransduction and mechanotransmission within (1) the sarcomere, (2) the intercalated disc, and (3) at the sarcolemma. The protein structures acting as mechanotransducers are the first step in the process that drives physiological and pathological cardiac hypertrophy and remodeling, as well as the transition to heart failure, and may provide better insights into mechanisms driving mechanotransduction-based diseases.