Acute slowing of cardiac conduction in response to myofibroblast coupling to cardiomyocytes through N-cadherin.
Acute slowing of cardiac conduction in response to myofibroblast coupling to cardiomyocytes through N-cadherin.
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DOI：
10.1016/j.yjmcc.2013.12.025
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发表时间：
2014-03
影响因子：
5
通讯作者：
Tung, Leslie
中科院分区：
文献类型：
--
作者：
Thompson, Susan A.;Blazeski, Adriana;Copeland, Craig R.;Cohen, Daniel M.;Chen, Christopher S.;Reich, Daniel M.;Tung, Leslie
心肌细胞和肌成纤维细胞相互作用的电生理后果尚不清楚，这两种细胞类型之间的机械偶联的贡献仍然知之甚少。在这项研究中，我们研究了由转化生长因子-β (TGF-β)激活的肌成纤维细胞的加入对新生大鼠心室单层细胞传导速度（CV）的影响的时间过程和机制。我们观察到肌成纤维细胞在接触30分钟内影响CV，并且这些影响与肌成纤维细胞引起的心肌细胞膜变形在时间上相关。在肌成纤维细胞中表达显性阴性RhoA会损害肌成纤维细胞收缩和肌成纤维细胞诱导的心脏传导减慢，而过表达组成型RhoA则几乎没有影响。为了确定这些细胞类型之间机械偶联的重要性，我们检测了心肌成纤维细胞和心肌细胞之间形成的细胞-细胞接触时心脏中两种主要钙粘蛋白（N-和ob -钙粘蛋白）的表达。虽然ob -钙粘蛋白经常在肌成纤维细胞-肌成纤维细胞接触处被发现，但在肌成纤维细胞-心肌细胞接触处很少被观察到表达。肌成纤维细胞诱导的心脏传导减慢不能通过沉默肌成纤维细胞中的OB-cadherin来阻止，并且可以通过机械敏感通道抑制剂（钆或链霉素）和细胞收缩抑制剂（blebbistatin）来逆转。相反，N-cadherin在肌成纤维细胞与心肌细胞接触时普遍表达，肌成纤维细胞中N-cadherin的沉默阻止了肌成纤维细胞依赖性的心脏传导减慢。我们认为肌成纤维细胞可以通过n -钙粘蛋白连接向心肌细胞膜施加收缩力，从而损害心脏组织的电生理功能。
The electrophysiological consequences of cardiomyocyte and myofibroblast interactions remain unclear, and the contribution of mechanical coupling between these two cell types is still poorly understood. In this study, we examined the time course and mechanisms by which addition of myofibroblasts activated by transforming growth factor-beta (TGF-β) influence the conduction velocity (CV) of neonatal rat ventricular cell monolayers. We observed that myofibroblasts affected CV within 30 minutes of contact and that these effects were temporally correlated with membrane deformation of cardiomyocytes by the myofibroblasts. Expression of dominant negative RhoA in the myofibroblasts impaired both myofibroblast contraction and myofibroblast-induced slowing of cardiac conduction, whereas overexpression of constitutive RhoA had little effect. To determine the importance of mechanical coupling between these cell types, we examined the expression of the two primary cadherins in the heart (N- and OB-cadherin) at cell-cell contacts formed between myofibroblasts and cardiomyocytes. Although OB-cadherin was frequently found at myofibroblast-myofibroblast contacts, very little expression was observed at myofibroblast-cardiomyocyte contacts. The myofibroblast-induced slowing of cardiac conduction was not prevented by silencing of OB-cadherin in the myofibroblasts, and could be reversed by inhibitors of mechanosensitive channels (gadolinium or streptomycin) and cellular contraction (blebbistatin). In contrast, N-cadherin expression was commonly observed at myofibroblast-cardiomyocyte contacts, and silencing of N-cadherin in myofibroblasts prevented the myofibroblast-dependent slowing of cardiac conduction. We propose that myofibroblasts can impair the electrophysiological function of cardiac tissue through the application of contractile force to the cardiomyocyte membrane via N-cadherin junctions.
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影响因子：
20.1
作者：
Angst, BD;Khan, LUR;Gourdie, RG
通讯作者：
Gourdie, RG
影响因子：
4
作者：
Pittet, Philippe;Lee, Kyumin;Hinz, Boris
通讯作者：
Hinz, Boris
DOI：
10.1073/pnas.0905349106
发表时间：
2009-07-14
影响因子：
11.1
作者：
Katsamba, P.;Carroll, K.;Honig, Barry H.
通讯作者：
Honig, Barry H.
DOI：
10.1073/pnas.0914547107
发表时间：
2010-06-01
影响因子：
11.1
作者：
Liu, Zhijun;Tan, John L.;Chen, Christopher S.
通讯作者：
Chen, Christopher S.
影响因子：
5
作者：
Kamkin, A;Kiseleva, I;Lab, MJ
通讯作者：
Lab, MJ