Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis.
Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis.
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DOI：
10.1093/cvr/cvw111
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发表时间：
2016-10
影响因子：
10.8
通讯作者：
Louch WE
中科院分区：
文献类型：
--
作者：
Frisk M;Ruud M;Espe EK;Aronsen JM;Røe ÅT;Zhang L;Norseng PA;Sejersted OM;Christensen GA;Sjaastad I;Louch WE
细胞膜的内陷称为t-小管是维持心室心肌细胞有效的兴奋-收缩偶联所必需的。心力衰竭期间t-小管结构的破坏与不同步、Ca 2+释放减缓和心跳功率降低有关。然而，其潜在机制尚不清楚。我们目前正在研究心室壁应力升高是否会触发t-小管结构和功能的重塑。采用MRI和血压测量来检查假手术和衰竭的梗死后大鼠心脏的左心室局部壁应力。在衰竭的心脏中，左心室舒张压升高和心室扩张导致室壁应力显著增加，特别是在靠近梗死的薄壁区域。近端区域的高室壁应力与二元锚连接蛋白-2表达减少和心肌细胞t管结构破坏有关。事实上，局部室壁应力测量可以预测假手术和衰竭心脏的t-小管密度。近端区的室壁应力升高和心肌细胞结构破坏也与心肌细胞中的去钙离子化Ca 2+释放相关，并显着降低体内局部收缩力。通过在培养条件下对乳头肌进行离体拉伸，确定了壁应力在促进t-小管重塑中的因果作用。与近端区体内观察到的壁应力水平相当的负荷降低了junctophilin-2的表达，促进了t-小管的丢失。升高的管壁应力减少了嗜连接蛋白-2的表达，并破坏了t管的完整性、Ca 2+释放和收缩功能。这些发现为室壁应力在促进心力衰竭进展中的作用提供了新的见解。
Invaginations of the cellular membrane called t-tubules are essential for maintaining efficient excitation–contraction coupling in ventricular cardiomyocytes. Disruption of t-tubule structure during heart failure has been linked to dyssynchronous, slowed Ca2+ release and reduced power of the heartbeat. The underlying mechanism is, however, unknown. We presently investigated whether elevated ventricular wall stress triggers remodelling of t-tubule structure and function. MRI and blood pressure measurements were employed to examine regional wall stress across the left ventricle of sham-operated and failing, post-infarction rat hearts. In failing hearts, elevated left ventricular diastolic pressure and ventricular dilation resulted in markedly increased wall stress, particularly in the thin-walled region proximal to the infarct. High wall stress in this proximal zone was associated with reduced expression of the dyadic anchor junctophilin-2 and disrupted cardiomyocyte t-tubular structure. Indeed, local wall stress measurements predicted t-tubule density across sham and failing hearts. Elevated wall stress and disrupted cardiomyocyte structure in the proximal zone were also associated with desynchronized Ca2+ release in cardiomyocytes and markedly reduced local contractility in vivo. A causative role of wall stress in promoting t-tubule remodelling was established by applying stretch to papillary muscles ex vivo under culture conditions. Loads comparable to wall stress levels observed in vivo in the proximal zone reduced expression of junctophilin-2 and promoted t-tubule loss. Elevated wall stress reduces junctophilin-2 expression and disrupts t-tubule integrity, Ca2+ release, and contractile function. These findings provide new insight into the role of wall stress in promoting heart failure progression.
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DOI：
10.1161/circheartfailure.110.958694
发表时间：
2011-03
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Landstrom AP;Kellen CA;Dixit SS;van Oort RJ;Garbino A;Weisleder N;Ma J;Wehrens XH;Ackerman MJ
通讯作者：
Ackerman MJ
影响因子：
3.4
作者：
Franzini-Armstrong, C;Protasi, F;Ramesh, V
通讯作者：
Ramesh, V
影响因子：
10.8
作者：
Mazhari, R;Omens, JH;McCulloch, AD
通讯作者：
McCulloch, AD
影响因子：
3.4
作者：
McNary, Thomas G.;Bridge, John H. B.;Sachse, Frank B.
通讯作者：
Sachse, Frank B.
DOI：
10.1186/1532-429x-15-82
发表时间：
2013-09-14
期刊：
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
影响因子：
--
作者：
Espe EK;Aronsen JM;Skårdal K;Schneider JE;Zhang L;Sjaastad I
通讯作者：
Sjaastad I