Department of Cardiac Electrophysiology, Imperial College & St. Mary's Hospital, London, UK.
J Cardiovasc Electrophysiol. 2010 Nov;21(11):1276-83. doi: 10.1111/j.1540-8167.2010.01802.x.
Effect of Stretch on Conduction and Cx43.
In disease states such as heart failure, myocardial infarction, and hypertrophy, changes in the expression and location of Connexin43 (Cx43) occur (Cx43 remodeling), and may predispose to arrhythmias. Stretch may be an important stimulus to Cx43 remodeling; however, it has only been investigated in neonatal cell cultures, which have different physiological properties than adult myocytes. We hypothesized that localized stretch in vivo causes Cx43 remodeling, with associated changes in conduction, mediated by the renin-angiotensin system (RAS).
In an open-chest canine model, a device was used to stretch part of the right ventricle (RV) by 22% for 6 hours. Activation mapping using a 312-electrode array was performed before and after stretch. Regional stretch did not change longitudinal conduction velocity (post-stretch vs baseline: 51.5 ± 5.2 vs 55.3 ± 8.1 cm/s, P = 0.24, n = 11), but significantly reduced transverse conduction velocity (28.7 ± 2.5 vs 35.4 ± 5.4 cm/s, P < 0.01). It also reduced total Cx43 expression, by Western blotting, compared with nonstretched RV of the same animal (86.1 ± 32.2 vs 100 ± 19.4%, P < 0.02, n = 11). Cx43 labeling redistributed to the lateral cell borders. Stretch caused a small but significant increase in the proportion of the dephosphorylated form of Cx43 (stretch 9.95 ± 1.4% vs control 8.74 ± 1.2%, P < 0.05). Olmesartan, an angiotensin II blocker, prevented the stretch-induced changes in Cx43 levels, localization, and conduction.
Myocardial stretch in vivo has opposite effects to that in neonatal myocytes in vitro. Stretch in vivo causes conduction changes associated with Cx43 remodeling that are likely caused by local stretch-induced activation of the RAS.
探讨牵张对传导和间隙连接蛋白 43（Cx43）的影响。
在心力衰竭、心肌梗死和肥厚等疾病状态下，Cx43 的表达和位置发生变化（Cx43 重构），可能导致心律失常。牵张可能是 Cx43 重构的重要刺激因素，但仅在新生细胞培养中进行了研究，而新生细胞培养的生理特性与成年心肌细胞不同。我们假设体内局部牵张导致 Cx43 重构，并通过肾素-血管紧张素系统（RAS）介导相关的传导变化。
在开胸犬模型中，使用一种装置将右心室（RV）的一部分牵张 22%，持续 6 小时。在牵张前后使用 312 电极阵列进行激活图绘制。区域牵张并未改变纵向传导速度（牵张后与基线相比：51.5 ± 5.2 对 55.3 ± 8.1 cm/s，P = 0.24，n = 11），但显著降低了横向传导速度（28.7 ± 2.5 对 35.4 ± 5.4 cm/s，P < 0.01）。与同一动物的未牵张 RV 相比，Western blot 显示其总 Cx43 表达也降低（86.1 ± 32.2 对 100 ± 19.4%，P < 0.02，n = 11）。Cx43 标记重新分布到细胞侧边界。牵张导致 Cx43 的去磷酸化形式比例略有但显著增加（牵张 9.95 ± 1.4%对对照 8.74 ± 1.2%，P < 0.05）。血管紧张素 II 阻滞剂奥美沙坦可防止牵张引起的 Cx43 水平、定位和传导变化。
体内心肌牵张与体外新生心肌细胞的作用相反。体内牵张导致与 Cx43 重构相关的传导变化，这可能是由局部牵张引起的 RAS 激活引起的。
