Apelin-13 Pretreatment Promotes the Cardioprotective Effect of Mesenchymal Stem Cells against Myocardial Infarction by Improving Their Survival.
Apelin-13 Pretreatment Promotes the Cardioprotective Effect of Mesenchymal Stem Cells against Myocardial Infarction by Improving Their Survival.
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Apelin-13预处理通过提高间充质干细胞的存活率促进其对心肌梗死的心脏保护作用
DOI：
10.1155/2022/3742678
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发表时间：
2022
影响因子：
4.3
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Chen G;Liang X;Han Q;Mai C;Shi L;Shao Z;Hong Y;Lin F;Li M;Hu B;Li X;Zhang Y
虽然基于间充质干细胞（MSC）的治疗已显示出对心肌梗死（MI）有希望的结果，但低细胞存活率严重限制了其有益效果。爱帕琳在细胞增殖中起着重要的调节作用。本研究旨在确定Apelin-13预处理是否可以改善缺血心脏中MSC的存活并增强其对MI的心脏保护功效。MSC用或不用爱帕琳-13预处理24小时，然后暴露于血清剥夺和缺氧（SD/H）48小时。MitoTracker染色观察骨髓间充质干细胞线粒体形态。TUNEL法检测MSCs凋亡情况。Mito-Sox染色检测MSCs线粒体活性氧（ROS）水平。将MSC和爱帕琳-13预处理的MSC移植到小鼠MI模型中的梗死周围区域中。Apelin-13预处理保护MSC免受SD/H诱导的线粒体断裂和凋亡。Apelin-13预处理减少了MSC中SD/H诱导的ROS产生。此外，Apelin-13预处理增强了SD/H条件下MSC的血管生成。从机制上讲，Apelin-13预处理通过激活ERK途径下调线粒体分裂来抑制SD/H诱导的MSC凋亡，并且这些作用被ERK抑制剂U 0126部分消除。Apelin-13预处理促进了缺血心脏中MSC的存活。此外，与MI后28天的MSC移植相比，Apelin-13预处理的MSC移植改善了心脏功能，增加了血管生成，并伴有纤维化减少。这些发现揭示了用Apelin-13预处理改善了MSC存活并增强了其对MI的治疗功效。我们的研究为改善基于MSC的心血管疾病治疗提供了一种新方法。
Although mesenchymal stem cell- (MSC-) based therapy has shown promising results for myocardial infarction (MI), low cell survival heavily limits its beneficial effects. Apelin plays an essential regulatory role in cell proliferation. This study was aimed at determining whether Apelin-13 pretreatment could improve the survival of MSCs in the ischemic heart and enhance their cardioprotective efficacy against MI. MSCs were pretreated with or without Apelin-13 for 24 hours and then exposed to serum deprivation and hypoxia (SD/H) for 48 hours. The mitochondrial morphology of MSCs was assessed by MitoTracker staining. The apoptosis of MSCs was determined by TUNEL staining. The level of mitochondrial reactive oxygen species (ROS) of MSCs was detected by Mito-Sox staining. MSCs and Apelin-13-pretreated MSCs were transplanted into the peri-infarct region in a mouse MI model. Apelin-13 pretreatment protected MSCs against SD/H-induced mitochondrial fragmentation and apoptosis. Apelin-13 pretreatment reduced ROS generation induced by SD/H in MSCs. Furthermore, Apelin-13 pretreatment enhanced the angiogenesis of MSCs under SD/H conditions. Mechanistically, Apelin-13 pretreatment inhibited SD/H-induced MSC apoptosis by downregulating mitochondrial fission via activation of the ERK pathway, and these effects were partially abrogated by ERK inhibitor U0126. Apelin-13 pretreatment promoted the survival of MSCs in the ischemic heart. Moreover, transplantation with Apelin-13-pretreated MSCs improved heart function and increased angiogenesis accompanied by decreased fibrosis compared with MSC transplantation at 28 days following MI. These findings reveal that pretreatment with Apelin-13 improves MSCs survival and enhances their therapeutic efficacy for MI. Our study provides a novel approach to improve MSC-based therapy for cardiovascular disease.
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影响因子：
4.6
作者：
Berta J;Török S;Tárnoki-Zách J;Drozdovszky O;Tóvári J;Paku S;Kovács I;Czirók A;Masri B;Megyesfalvi Z;Oskolás H;Malm J;Ingvar C;Markó-Varga G;Döme B;László V
通讯作者：
László V
DOI：
10.1007/978-1-4939-3584-0_17
发表时间：
2016-01-01
期刊：
MESENCHYMAL STEM CELLS, 2 EDITION
影响因子：
--
作者：
Lian, Qizhou;Zhang, Yuelin;Tse, Hung-Fat
通讯作者：
Tse, Hung-Fat
影响因子：
13
作者：
Kittleson, Michelle M.;Kobashigawa, Jon A.
通讯作者：
Kobashigawa, Jon A.
SIRT4 通过 ERK-Drp1 通路介导的线粒体动力学抑制 NSCLC 的恶性进展
影响因子：
8
作者：
Fu, L.;Dong, Q.;Li, Q.
通讯作者：
Li, Q.
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影响因子：
12.4
作者：
Hu HF;Xu WW;Li YJ;He Y;Zhang WX;Liao L;Zhang QH;Han L;Yin XF;Zhao XX;Pan YL;Li B;He QY
通讯作者：
He QY