Emergence of Mechano-Sensitive Contraction Autoregulation in Cardiomyocytes.
Emergence of Mechano-Sensitive Contraction Autoregulation in Cardiomyocytes.
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DOI：
10.3390/life11060503
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发表时间：
2021-05-29
期刊：
影响因子：
--
通讯作者：
Chen-Izu Y
中科院分区：
文献类型：
--
作者：
Izu L;Shimkunas R;Jian Z;Hegyi B;Kazemi-Lari M;Baker A;Shaw J;Banyasz T;Chen-Izu Y
心脏具有两种增强收缩强度的内在机制，其补偿增加的机械负荷以帮助维持心输出量。当血管阻力增加时，心室腔最初扩张，通过Frank-Starling机制引起收缩力的立即长度依赖性增加。此外，应力依赖性Anrep效应缓慢增加收缩力，导致腔室体积恢复到其初始状态。Anrep效应提出了一个悖论：即使在细胞长度恢复其初始长度后，心肌细胞如何保持较高的收缩力？在这里，我们提出了一个表面力学传感器模型，使心肌细胞在相同的机械应变感测不同的机械应力。细胞表面机械传感器耦合到机械化学转导反馈机制，涉及三个要素：表面机械传感器应变，细胞内瞬态，和细胞应变。我们发现，在这个简单而通用的系统中，收缩性自动调节自然出现，使心肌细胞能够保持收缩幅度，尽管在一系列后负荷的变化。这些非平凡的模型预测已被实验证实。因此，该模型为理解心肌细胞的收缩性自动调节提供了一个新的概念框架，这有助于心脏对健康和疾病中机械负荷变化的内在适应性。
The heart has two intrinsic mechanisms to enhance contractile strength that compensate for increased mechanical load to help maintain cardiac output. When vascular resistance increases the ventricular chamber initially expands causing an immediate length-dependent increase of contraction force via the Frank-Starling mechanism. Additionally, the stress-dependent Anrep effect slowly increases contraction force that results in the recovery of the chamber volume towards its initial state. The Anrep effect poses a paradox: how can the cardiomyocyte maintain higher contractility even after the cell length has recovered its initial length? Here we propose a surface mechanosensor model that enables the cardiomyocyte to sense different mechanical stresses at the same mechanical strain. The cell-surface mechanosensor is coupled to a mechano-chemo-transduction feedback mechanism involving three elements: surface mechanosensor strain, intracellular transient, and cell strain. We show that in this simple yet general system, contractility autoregulation naturally emerges, enabling the cardiomyocyte to maintain contraction amplitude despite changes in a range of afterloads. These nontrivial model predictions have been experimentally confirmed. Hence, this model provides a new conceptual framework for understanding the contractility autoregulation in cardiomyocytes, which contributes to the heart’s intrinsic adaptivity to mechanical load changes in health and diseases.
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影响因子：
20.1
作者：
Alvarez, BV;Pérez, NG;Cingolani, HE
通讯作者：
Cingolani, HE
影响因子：
--
作者：
DONALD, TC;PETERSON, DM;HEFNER, LL
通讯作者：
HEFNER, LL
DOI：
10.1016/0735-1097(94)00562-5
发表时间：
1995-05-01
影响因子：
24
作者：
KLAUTZ, RJM;TEITEL, DF;BAAN, J
通讯作者：
BAAN, J
影响因子：
7.3
作者：
Jian Z;Han H;Zhang T;Puglisi J;Izu LT;Shaw JA;Onofiok E;Erickson JR;Chen YJ;Horvath B;Shimkunas R;Xiao W;Li Y;Pan T;Chan J;Banyasz T;Tardiff JC;Chiamvimonvat N;Bers DM;Lam KS;Chen-Izu Y
通讯作者：
Chen-Izu Y
影响因子：
3.4
作者：
Niederer, Steven A.;Smith, Nicolas P.
通讯作者：
Smith, Nicolas P.