Experimental Cardiology, Thoraxcenter, Cardiovascular Research School COEUR, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
J Mol Cell Cardiol. 2011 Jun;50(6):1017-25. doi: 10.1016/j.yjmcc.2011.01.016. Epub 2011 Feb 1.
There is ample evidence that regular exercise exerts beneficial effects on left ventricular (LV) hypertrophy, remodeling and dysfunction produced by ischemic heart disease or systemic hypertension. In contrast, the effects of exercise on pathological LV hypertrophy and dysfunction produced by LV outflow obstruction have not been studied to date. Consequently, we evaluated the effects of 8 weeks of voluntary wheel running in mice (which mitigates post-infarct LV dysfunction) on LV hypertrophy and dysfunction produced by mild (mTAC) and severe (sTAC) transverse aortic constriction. mTAC produced ~40% LV hypertrophy and increased myocardial expression of hypertrophy marker genes but did not affect LV function, SERCA2a protein levels, apoptosis or capillary density. Exercise had no effect on global LV hypertrophy and function in mTAC but increased interstitial collagen, and ANP expression. sTAC produced ~80% LV hypertrophy and further increased ANP expression and interstitial fibrosis and, in contrast with mTAC, also produced LV dilation, systolic as well as diastolic dysfunction, pulmonary congestion, apoptosis and capillary rarefaction and decreased SERCA2a and ryanodine receptor (RyR) protein levels. LV diastolic dysfunction was likely aggravated by elevated passive isometric force and Ca(2+)-sensitivity of myofilaments. Exercise training failed to mitigate the sTAC-induced LV hypertrophy and capillary rarefaction or the decreases in SERCA2a and RyR. Exercise attenuated the sTAC-induced increase in passive isometric force but did not affect myofilament Ca(2+)-sensitivity and tended to aggravate interstitial fibrosis. In conclusion, exercise had no effect on LV function in compensated and decompensated cardiac hypertrophy produced by LV outflow obstruction, suggesting that the effect of exercise on pathologic LV hypertrophy and dysfunction depends critically on the underlying cause.
有充分的证据表明，规律的运动对缺血性心脏病或系统性高血压引起的左心室（LV）肥大、重构和功能障碍有有益的影响。相比之下，运动对 LV 流出道梗阻引起的病理性 LV 肥大和功能障碍的影响尚未得到研究。因此，我们评估了 8 周的自愿轮跑（减轻梗死后 LV 功能障碍）对轻度（mTAC）和重度（sTAC）横主动脉缩窄引起的 LV 肥大和功能障碍的影响。mTAC 导致约 40%的 LV 肥大和增加心肌肥大标志物基因的表达，但不影响 LV 功能、SERCA2a 蛋白水平、细胞凋亡或毛细血管密度。运动对 mTAC 中的整体 LV 肥大和功能没有影响，但增加了间质胶原和 ANP 的表达。sTAC 导致约 80%的 LV 肥大，并进一步增加了 ANP 表达和间质纤维化，与 mTAC 相反，还导致 LV 扩张、收缩和舒张功能障碍、肺水肿、细胞凋亡和毛细血管稀疏以及 SERCA2a 和 RyR 蛋白水平降低。LV 舒张功能障碍可能是由于被动等长力升高和肌球蛋白钙敏感性增加而加重。运动训练未能减轻 sTAC 引起的 LV 肥大和毛细血管稀疏，也不能降低 SERCA2a 和 RyR。运动减轻了 sTAC 引起的被动等长力增加，但不影响肌球蛋白钙敏感性，并倾向于加重间质纤维化。总之，运动对 LV 流出道梗阻引起的代偿性和失代偿性 LV 肥大的 LV 功能没有影响，这表明运动对病理性 LV 肥大和功能障碍的影响取决于潜在的原因。
