Thymosin beta4: a key factor for protective effects of eEPCs in acute and chronic ischemia.

Thymosin beta4: a key factor for protective effects of eEPCs in acute and chronic ischemia.
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DOI:
10.1111/j.1749-6632.2010.05489.x
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发表时间:
2010-04
影响因子:
5.2
通讯作者:
Kupatt C
Kupatt C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hinkel R;Bock-Marquette I;Hatzopoulos AK;Kupatt C

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急性心肌梗塞仍然是工业化国家的主要死亡原因之一。即使在成功的血运重建后,心肌缺血也会导致心肌细胞的损失和瘢痕形成。将胚胎EPCs(eEPCs)回输到猪心脏的缺血区域,以PI-3 K/Akt依赖的方式对急性和慢性缺血提供快速旁分泌益处。在急性心肌缺血模型中,应用eEPC后梗死面积和局部心肌功能丧失减少,除非进行胸腺素β4 shRNA细胞预处理。胸腺素β4肽逆向输注模拟了eEPC衍生的梗死面积和心肌功能的改善。在慢性缺血(兔模型)中,回输到缺血后肢的eEPCs增强毛细血管密度,侧支生长和灌注。在应用前将胸腺素β4 shRNA导入eEPCs,不存在治疗性新生血管。结论:eEPCs具有胸腺素β4依赖性的急性和慢性缺血保护作用。
Acute myocardial infarction is still one of the leading causes of death in the industrial nations. Even after successful revascularization, myocardial ischemia results in a loss of cardiomyocytes and scar formation. Embryonic EPCs (eEPCs), retroinfused into the ischemic region of the pig heart, provided rapid paracrine benefit to acute and chronic ischemia in a PI-3K/Akt-dependent manner. In a model of acute myocardial ischemia, infarct size and loss of regional myocardial function decreased after eEPC application, unless cell pre-treatment with thymosin β4 shRNA was performed. Thymosin β4 peptide retroinfusion mimicked the eEPC-derived improvement of infarct size and myocardial function. In chronic ischemia (rabbit model), eEPCs retroinfused into the ischemic hindlimb enhanced capillary density, collateral growth, and perfusion. Therapeutic neovascularization was absent when thymosin β4 shRNA was introduced into eEPCs before application. In conclusion, eEPCs are capable of acute and chronic ischemia protection in a thymosin β4 dependent manner.
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