Autophagy-mediated degradation is necessary for regression of cardiac hypertrophy during ventricular unloading
Autophagy-mediated degradation is necessary for regression of cardiac hypertrophy during ventricular unloading
复制标题
DOI：
10.1016/j.bbrc.2013.10.135
复制
发表时间：
2013-11-29
影响因子：
3.1
通讯作者：
Otsu, Kinya
中科院分区：
文献类型：
--
作者：
Oyabu, Jota;Yamaguchi, Osamu;Otsu, Kinya
心脏肥大是对各种压力的反应，作为维持心输出量和室壁压力正常化的补偿机制。预防或消退心脏肥大可能是主要的治疗目标。尽管在控制病因后心肌肥厚会发生消退，但其分子机制仍有待阐明。在本研究中，我们研究了自噬在心肌肥厚消退中的作用。野生型小鼠在使用微型渗透泵连续输注血管紧张素II 14天后显示出心脏肥大，并且在去除微型泵7天后观察到心脏肥大的消退。自噬在心脏肥大消退过程中被诱导，微管相关蛋白 1 轻链 3 (LC3)-II 蛋白水平增加证明了这一点。然后，我们对心脏特异性 Atg5 缺陷 (CKO) 和对照小鼠 (CTL) 进行血管紧张素 II 输注 14 天。 CKO 和 CTL 出现相似程度的心脏肥大，但没有收缩功能障碍。移除微型泵 7 天后，与 CTL 相比，CKO 的心脏肥大消退明显较少。在 CKO 中，卸载后压力超负荷引起的心脏肥大的消退也减弱。这些结果表明，在神经体液和血流动力学应激卸载过程中，自噬对于心肌肥大的消退是必要的。 (C) 2013 年，爱思唯尔公司出版。
Cardiac hypertrophy occurs in response to a variety of stresses as a compensatory mechanism to maintain cardiac output and normalize wall stress. Prevention or regression of cardiac hypertrophy can be a major therapeutic target. Although regression of cardiac hypertrophy occurs after control of etiological factors, the molecular mechanisms remain to be clarified. In the present study, we investigated the role of autophagy in regression of cardiac hypertrophy. Wild-type mice showed cardiac hypertrophy after continuous infusion of angiotensin II for 14 days using osmotic minipumps, and regression of cardiac hypertrophy was observed 7 days after removal of the minipumps. Autophagy was induced during regression of cardiac hypertrophy, as evidenced by an increase in microtubule-associated protein 1 light chain 3 (LC3)-II protein level. Then, we subjected cardiac-specific Atg5-deficient (CKO) and control mice (CTL) to angiotensin II infusion for 14 days. CKO and CTL developed cardiac hypertrophy to a similar degree without contractile dysfunction. Seven days after removal of the minipumps, CKO showed significantly less regression of cardiac hypertrophy compared with CTL. Regression of pressure overload-induced cardiac hypertrophy after unloading was also attenuated in CKO. These results suggest that autophagy is necessary for regression of cardiac hypertrophy during unloading of neurohumoral and hemodynamic stress. (C) 2013 Published by Elsevier Inc.