Hanna Nessrine, Cardin Sophie, Leung Tack-Ki, Nattel Stanley
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Cardiovasc Res. 2004 Aug 1;63(2):236-44. doi: 10.1016/j.cardiores.2004.03.026.
Congestive heart failure (CHF) causes arrhythmogenic remodeling in both atria and ventricles, but differences between atrial and ventricular remodeling in CHF have not been well characterized.
We examined atrial and ventricular tissues from dogs with CHF induced by ventricular tachypacing (220-240/min) for 0 (control) or 24 h, or 1, 2 or 5 weeks. Histopathology was used to assess apoptosis, fibrosis, white blood cell infiltration and cell death, ELISA to measure angiotensin-II concentration and Western blot to evaluate protein expression. Ventricular tachypacing-induced CHF was associated with substantially more fibrosis in left atrium (maximum 10 +/- 1% at 5 weeks) than in left ventricle (0.4 +/- 0.1% at 5 weeks, P < 0.01 versus left atrium). Tissue angiotensin-II concentration increased to steady state in atrial tissue at 24 h but increased more slowly in left ventricle, with a maximum that was significantly higher in atrium than ventricle. Ventricular tachypacing caused tissue apoptosis, inflammatory cell infiltration and cell death, with maximum changes in left atrium being faster, transient and larger than in left ventricle. Mitogen activated protein kinase activation was rapid (within 24 h) in left atrium, but smaller and slower (p38, c-Jun N-terminal kinase) or non-significant (extracellular signal-related kinase) in left ventricle. The 25-kDa activated form of transforming growth factor-beta1, a particularly important profibrotic mediator in atrium, increased significantly in left atrium, from 2.6 +/- 0.6 (control) to 9.2 +/- 1.7 (24 h) and 8.1 +/- 1.8 optical density units (1 week), but was not significantly changed in ventricle.
There are qualitative and quantitative differences in atrial versus ventricular remodeling in experimental ventricular tachypacing-induced CHF, with potentially important consequences for understanding underlying mechanisms and developing new therapeutic approaches.
充血性心力衰竭（CHF）会导致心房和心室发生致心律失常性重构，但CHF中心房和心室重构之间的差异尚未得到充分表征。
我们检查了通过心室快速起搏（220 - 240次/分钟）诱导CHF 0（对照）、24小时、或1、2或5周的犬的心房和心室组织。采用组织病理学评估细胞凋亡、纤维化、白细胞浸润和细胞死亡情况，用酶联免疫吸附测定法（ELISA）测量血管紧张素-II浓度，用蛋白质印迹法评估蛋白质表达。心室快速起搏诱导的CHF与左心房（5周时最高达10±1%）相比左心室（5周时为0.4±0.1%，与左心房相比P<0.01）出现更多的纤维化。组织血管紧张素-II浓度在心房组织中24小时达到稳态，但在左心室中升高较慢，其最高值在心房显著高于心室。心室快速起搏导致组织细胞凋亡、炎性细胞浸润和细胞死亡，左心房的最大变化比左心室更快、更短暂且更大。丝裂原活化蛋白激酶在左心房中迅速激活（24小时内），但在左心室中较小且较慢（p38、c-Jun氨基末端激酶）或无显著变化（细胞外信号调节激酶）。转化生长因子-β1的25 kDa活化形式，是心房中一种特别重要的促纤维化介质，在左心房中显著增加，从2.6±0.6（对照）增至9.2±1.7（24小时）和8.1±1.8光密度单位（1周），但在心室中无显著变化。
在实验性心室快速起搏诱导的CHF中，心房与心室重构存在质和量的差异，这对于理解潜在机制和开发新的治疗方法可能具有重要意义。
