Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction
Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction
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DOI：
10.1016/j.ijcard.2014.10.144
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发表时间：
2015-01-15
影响因子：
3.5
通讯作者：
Iwao, Hiroshi
中科院分区：
文献类型：
--
作者：
Yamaguchi, Takehiro;Izumi, Yasukatsu;Iwao, Hiroshi
背景：反复治疗短暂性肢体缺血的远程缺血预适应(RIC)是一种临床适用的再灌流时保护心脏免受损伤的方法。方法和结果：在心肌梗死后4周，将大鼠分为未治疗组(UT)和RIC治疗组。RIC治疗采用双侧后肢缺血5min+再灌流5min，每日1次，共5个周期，共4周。尽管心肌梗死大小相似，但RIC组与UT组相比，左室射血分数(LVEF)显著改善。此外，RIC组的LVEF在治疗后有所改善，但并不显著。RIC治疗也可防止左室舒张功能的恶化。RIC治疗可显著减轻MI诱导的交界区LV间质纤维化和氧化应激。组织纤维化的关键调节因子microRNA-29a(miR-29a)在RIC组的外体和边缘区高表达。即使在分化的C2C12来源的外体中，miR-29a在低氧条件下的表达也显著增加。与miR-29a一样，胰岛素样生长因子1受体(IGF-1R)在RIC组的外体和远端非梗死区心肌中均有高表达。在低氧条件下，C2C12来源的外切体中IGF-1R的表达也增加。结论：重复RIC可减少MI所致的不良左室重构和氧化应激。外切体介导的细胞间通讯可能有助于RIC治疗的有益效果。(C)2014爱思唯尔爱尔兰有限公司。保留所有权利。
Background: Remote ischemic conditioning (RIC) by repeated treatment of transient limb ischemia is a clinically applicable method for protecting the heart against injury at the time of reperfusion. In this study, we investigated the effects of repeated RIC on cardiac dysfunction after myocardial infarction (MI).Methods and results: At 4 weeks after MI, rats were separated into the untreated (UT) group or the RIC-treated group. RIC treatment was performed by 5 cycles of 5 min of bilateral hindlimb ischemia and 5 min of reperfusion once a day for 4 weeks. Despite comparable MI size, left ventricular (LV) ejection fraction (LVEF) was significantly improved in the RIC group compared with the UT group. Furthermore, the LVEF in the RIC group was improved, although not significantly, after treatment. RIC treatment also prevented the deterioration of LV diastolic function. MI-induced LV interstitial fibrosis in the boundary region and oxidant stress were significantly attenuated by RIC treatment. MicroRNA-29a (miR-29a), a key regulator of tissue fibrosis, was highly expressed in the exosomes and the marginal area of the RIC group. Even in the differentiated C2C12-derived exosomes, miR-29a expression was significantly increased under hypoxic condition. As well as miR-29a, insulin-like growth factor 1 receptor (IGF-1R) was highly expressed both in the exosomes and remote non-infarcted myocardium of the RIC group. IGF-1R expression was also increased in the C2C12-derived exosomes under hypoxic conditions.Conclusions: Repeated RIC reduces adverse LV remodeling and oxidative stress by MI. Exosome-mediated intercellular communication may contribute to the beneficial effect of RIC treatment. (C) 2014 Elsevier Ireland Ltd. All rights reserved.