TPPU enhanced exercise‐induced epoxyeicosatrienoic acid concentrations to exert cardioprotection in mice after myocardial infarction

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 (TPP...

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Published in:Journal of cellular and molecular medicine 2018-03, Vol.22 (3), p.1489-1500
Main Authors: Guo, Yuan, Luo, Fei, Zhang, Xv, Chen, Jingyuan, Shen, Li, Zhu, Yi, Xu, Danyan
Format: Article
Language:English
Subjects:
Acids
AKT protein
Angiogenesis
Bone marrow
Cell culture
endothelial progenitor cells
Epoxide hydrolase
Exercise
Glycogen
Glycogen synthase kinase 3
Heart
Heart attacks
Heart diseases
Infarction
Kinases
Mice
microRNA‐126
miRNA
Myocardial infarction
Original
Osteoprogenitor cells
Signal transduction
soluble epoxide hydrolase inhibitor
Surgery
Urea
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Summary: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.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.13412