TPPU enhanced exercise-induced epoxyeicosatrienoic acid concentrations to exert cardioprotection in mice after myocardial infarction.
TPPU enhanced exercise-induced epoxyeicosatrienoic acid concentrations to exert cardioprotection in mice after myocardial infarction.
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TPPU 提高运动诱导的环氧二十碳三烯酸浓度，对心肌梗塞后的小鼠发挥心脏保护作用
DOI：
10.1111/jcmm.13412
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发表时间：
2018-03
影响因子：
5.3
通讯作者：
Xu D
中科院分区：
文献类型：
--
作者：
Guo Y;Luo F;Zhang X;Chen J;Shen L;Zhu Y;Xu D
运动训练（ET）是治疗心肌梗死（MI）的一种安全有效的方法。鉴于运动的众多益处，运动诱导的介质可能是MI有希望的治疗靶点。C57 BL/6小鼠在接受MI手术前1周喂食1-三氟甲氧基苯基-3-（1-丙酰基哌啶-4-基）脲（TPPU），一种新型可溶性环氧化物水解酶抑制剂（sEHI），以增加环氧二十碳三烯酸（EET）水平。恢复1周后，小鼠遵循规定的运动计划。在运动4周后从小鼠中分离骨髓来源的内皮祖细胞（EPC）并培养7天。测量缺血区域周围的血管生成、EPC功能以及microRNA-126（miR-126）及其靶基因Spread 1的表达。通过在EPC培养基中加入TPPU，在体外证实了结果。ET可显著增加MI后血清EET水平，促进血管新生。TPPU可增强ET缩小心肌梗死面积、改善心功能的作用。ET增加EPC功能和miR-126表达，TPPU进一步增强，而Spread 1表达显著下调。此外，蛋白激酶B/糖原合成酶激酶3β（AKT/GSK 3 β）信号通路在给予TPPU后被激活。在MI后小鼠中，EAE是运动诱导的心脏保护的潜在介质。TPPU通过增加EET水平和促进缺血区域周围的血管生成，增强MI后小鼠运动诱导的心脏恢复。
Exercise training (ET) is a safe and efficacious therapeutic approach for myocardial infarction (MI). Given the numerous benefits of exercise, exercise‐induced mediators may be promising treatment targets for MI. C57BL/6 mice were fed 1‐trifluoromethoxyphenyl‐3‐(1‐propionylpiperidine‐4‐yl) urea (TPPU), a novel soluble epoxide hydrolase inhibitor (sEHI), to increase epoxyeicosatrienoic acid (EET) levels, for 1 week before undergoing MI surgery. After 1‐week recovery, the mice followed a prescribed exercise programme. Bone marrow‐derived endothelial progenitor cells (EPCs) were isolated from the mice after 4 weeks of exercise and cultured for 7 days. Angiogenesis around the ischaemic area, EPC functions, and the expression of microRNA‐126 (miR‐126) and its target gene Spred1 were measured. The results were confirmed in vitro by adding TPPU to EPC culture medium. ET significantly increased serum EET levels and promoted angiogenesis after MI. TPPU enhanced the effects of ET to reduce the infarct area and improve cardiac function after MI. ET increased EPC function and miR‐126 expression, which were further enhanced by TPPU, while Spred1 expression was significantly down‐regulated. Additionally, the protein kinase B/glycogen synthase kinase 3β (AKT/GSK3β) signalling pathway was activated after the administration of TPPU. EETs are a potential mediator of exercise‐induced cardioprotection in mice after MI. TPPU enhances exercise‐induced cardiac recovery in mice after MI by increasing EET levels and promoting angiogenesis around the ischaemic area.
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影响因子：
6.7
作者：
Cesari, Francesca;Marcucci, Rossella;Fattirolli, Francesco
通讯作者：
Fattirolli, Francesco
影响因子：
4.4
作者：
Qu, You-Yang;Yuan, Mei-Yan;Zhu, Yu-Lan
通讯作者：
Zhu, Yu-Lan
影响因子：
2.9
作者：
Ostermann AI;Herbers J;Willenberg I;Chen R;Hwang SH;Greite R;Morisseau C;Gueler F;Hammock BD;Schebb NH
通讯作者：
Schebb NH
影响因子：
--
作者：
Tao L;Bei Y;Zhang H;Xiao J;Li X
通讯作者：
Li X
影响因子：
7.3
作者：
Rose TE;Morisseau C;Liu JY;Inceoglu B;Jones PD;Sanborn JR;Hammock BD
通讯作者：
Hammock BD