Activation of cardiac adenylyl cyclase expression increases function of the failing ischemic heart in mice
Activation of cardiac adenylyl cyclase expression increases function of the failing ischemic heart in mice
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DOI：
10.1016/j.jacc.2008.01.015
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发表时间：
2008-04-15
影响因子：
24
通讯作者：
Hammond, H. Kirk
中科院分区：
文献类型：
--
作者：
Lai, N. Chin;Tang, Tong;Hammond, H. Kirk
目的 本研究旨在评估在出现严重充血性心力衰竭（CHF）时，增加左心室（LV）腺苷酸环化酶VI（AC(VI)）的表达是否会增强处于衰竭状态的心脏的功能。
背景 在小鼠急性心肌梗死（MI）后，左心室AC(VI)含量增加可显著降低死亡率并提高左心室功能。然而，在缺血性心肌病导致的严重心力衰竭情况下，心脏AC(VI)含量增加的影响尚不明确。
方法 对心脏定向且受调控表达AC(VI)的小鼠进行冠状动脉结扎，5周后诱导出严重的CHF。然后在一组（AC - On组）激活AC(VI)表达，而在另一组（AC - Off组）不激活。5周后获取多项左心室收缩和舒张功能指标，并评估左心室样本中钙和β - 肾上腺素能受体信号传导、细胞凋亡以及心肌肌钙蛋白I磷酸化的变化。
结果 AC(VI)表达激活5周后，左心室收缩和舒张功能增强。左心室功能改善与心肌肌钙蛋白I磷酸化正常化以及细胞凋亡减少有关。
结论 在患有缺血性心肌病和严重CHF的小鼠中激活心脏AC(VI)表达可改善衰竭心脏的功能。
Objectives This study sought to evaluate whether increased left ventricular (LV) adenylyl cyclase VI (AC(VI)) expression, at a time when severe congestive heart failure (CHF) was present, would increase function of the actively failing heart.Background Increased LV AC(VI) content markedly reduces mortality and increases LV function after acute myocardial infarction (MI) in mice. However, the effects of increased cardiac AC(VI) content in the setting of severe heart failure caused by ischemic cardiomyopathy are unknown.Methods Mice with cardiac-directed and regulated expression of AC(VI) underwent coronary artery ligation to induce severe CHF 5 weeks later. AC(VI) expression was then activated in 1 group (AC-On) but not the other (AC-Off). Multiple measures of LV systolic and diastolic function were obtained 5 weeks later, and LV samples were assessed for alterations in calcium and beta-adrenergic receptor signaling, apoptosis, and cardiac troponin I phosphorylation.Results The LV systolic and diastolic function was increased 5 weeks after activation of AC(VI) expression. Improved LV function was associated with normalization of cardiac troponin I phosphorylation and reduced apoptosis.Conclusions Activation of cardiac AC(VI) expression in mice with ischemic cardiomyopathy and severe CHF improves function of the failing heart.