MSC exosome-mediated cardioprotection in ischemic mouse heart comparative proteomics of infarct and peri-infarct areas.
MSC exosome-mediated cardioprotection in ischemic mouse heart comparative proteomics of infarct and peri-infarct areas.
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DOI：
10.1007/s11010-020-04029-6
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发表时间：
2021-04
影响因子：
4.3
通讯作者：
Mehta JL
中科院分区：
文献类型：
--
作者：
Kore RA;Wang X;Ding Z;Griffin RJ;Tackett AJ;Mehta JL
在缺血动物模型中，间充质干细胞（MSC）外泌体可能限制心脏损伤，甚至逆转心脏损伤。为了了解外泌体介导的心功能改善，我们检查了MSC外泌体处理的左冠状动脉（LCA）结扎小鼠心脏的蛋白质组学改变，特别强调梗死周围区域。结扎LCA后7 d，观察小鼠左室收缩末期厚度、梗死面积及存活率。质谱分析梗死区和梗死周围区域。Western blot和免疫荧光检测炎症标志物（LOX-1、NLRP3）和细胞死亡标志物（Bax、Bcl-2、Caspases 1、3、GSDMD）的表达。对盐处理心脏梗死区和梗死周围区域的蛋白质组学分析揭示了参与炎症和凋亡细胞死亡的差异表达蛋白，同时显示控制细胞死亡的过程耗竭。外泌体治疗显著改善了梗死区和梗死周围区域的蛋白质组学特征，在梗死周围区域更是如此。外泌体处理小鼠的梗死面积更小（9±1%），心肌收缩功能（部分缩短）得以保留（28±2%）。外泌体处理小鼠的存活率也较好。骨髓间充质干细胞外泌体显著降低梗死区及梗死区周围的白细胞积累、LOX-1和NLRP3炎性体的表达以及细胞死亡标志物（cleaved Caspase-3、Caspase-1、GSDMD、Bcl-2和Bax）的表达（均P<0.01）。在培养的原代小鼠心肌细胞中，MSC外泌体处理基本上逆转了炎症诱导的促凋亡和炎症信号（P<0.01）。MSC外泌体通过抑制炎症和促凋亡过程发挥其心脏保护作用，特别是在梗死周围区域，导致LCA结扎后心脏功能的保存。
Mesenchymal stem cell (MSC) exosomes may limit cardiac injury, and even reverse cardiac damage in animal models of ischemia. To understand exosome-mediated improvement in cardiac function we examined the proteomic alternations in the MSC exosome-treated mice hearts subjected to left coronary artery (LCA) ligation, with particular emphasis on peri-infarct areas. At 7 days after LCA ligation, left ventricular end systolic thickness, infarct size and survival of mice were studied. Mass spectrometric analysis of infarct and peri-infarct areas was carried out. Expression of inflammatory markers (LOX-1 and NLRP3) and cell death markers (Bax, Bcl-2, Caspases 1 and 3 and GSDMD) were investigated by Western blots and immunofluorescence. Proteomic analysis of the infarct and peri-infarct areas in saline-treated hearts revealed differentially expressed proteins involved in inflammation and apoptotic cell death, while showing depletion of processes governing cell death. Exosome treatment significantly improved the proteomic profile in both infarct and peri-infarct areas, more so in the peri-infarct areas. The infarct size was smaller (9±1 %), and cardiac contractile function (fractional shortening) was preserved in the exosome-treated mice (28±2 %). Survival of exosome-treated mice was also better. White blood cell accumulation in and around the infarct area, expression of LOX-1 and NLRP3 inflammasome, and markers of cell death (cleaved Caspase-3, Caspase-1, GSDMD, Bcl-2 and Bax) were dramatically reduced by MSC exosome treatment (all P<0.01). In cultured primary mouse cardiomyocytes, treatment with MSC exosomes essentially reversed inflammation-induced pro-apoptotic and inflammatory signals (P<0.01). MSC exosomes exert their cardioprotective effects by suppressing inflammation and pro-apoptotic processes, particularly in the peri-infarct areas, resulting in preservation of cardiac function after LCA ligation.
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影响因子：
37.8
作者：
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
4.6
作者：
Kore, Rajshekhar A.;Henson, Jeffrey C.;Mehta, Jawahar L.
通讯作者：
Mehta, Jawahar L.
影响因子：
5
作者：
Luther, Kristin M.;Haar, Lauren;Jones, W. Keith
通讯作者：
Jones, W. Keith
影响因子：
5
作者：
Hu, Changping;Chen, Jiawei;Mehta, Jawahar L.
通讯作者：
Mehta, Jawahar L.
影响因子：
37.8
作者：
Go, Alan S.;Mozaffarian, Dariush;Turner, Melanie B.
通讯作者：
Turner, Melanie B.