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Apelin protects against myocardial ischemic injury by inhibiting dynamin-related protein 1

It is known that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission plays an important role in ischemic injury of myocardial infarction (MI). Apelin, an endogenous ligand for Apelin receptor, acts as a key modulator of cardiovascular diseases. Here, we examined the effects of Apelin on...

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Published in:Oncotarget 2017-11, Vol.8 (59), p.100034-100044
Main Authors: Xu, Wei, Yu, Hongwei, Ma, Ruixue, Ma, Lina, Liu, Qiushuang, Shan, Huitong, Wu, Chengyu, Zhang, Rong, Zhou, Yuhong, Shan, Hongli
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cited_by cdi_FETCH-LOGICAL-c399t-da02ad0f933cc5fb9bb8379883628ce451d4dd487c34750558882283db1330133
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container_issue 59
container_start_page 100034
container_title Oncotarget
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creator Xu, Wei
Yu, Hongwei
Ma, Ruixue
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description It is known that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission plays an important role in ischemic injury of myocardial infarction (MI). Apelin, an endogenous ligand for Apelin receptor, acts as a key modulator of cardiovascular diseases. Here, we examined the effects of Apelin on MI injury and underlying mechanisms. Adult male C57BL/6J mice were treated with Apelin for 4 weeks and then subjected coronary artery ligation (LAD) to induce MI and the protective effects of Apelin on MI injury were evaluated at 6 h post LAD. Mitochondrial fission was significantly increased in MI as evidenced by enhanced expression of phosphorylated Drp1 (p-Drp1 ) without affecting total Drp-1 level and degenerative transformation of mitochondria into short rods as typical fission. Apelin markedly inhibited p-Drp1 and preserved mitochondrial morphology in MI. Similar effects of Apelin were consistently observed in primary cultured cardiomyocytes under hypoxia. Apelin decreased hypoxia-induced cardiomyocyte apoptosis as evidenced by decreased TUNEL-positive cells and preserved mitochondrial membrane potential (MMP). Apelin decreased Bax/Bcl-2 ratio and limited the release of cytochrome C and activation of caspase-9 and caspase-3 both and . Finally, Apelin diminished the infarct size and normalized the impaired cardiac function as indicated by rescuing of the decreased ejection faction and fractional shortening in MI mice. In conclusion, Apelin prevented mitochondrial fission by inhibiting p-Drp1 , which prevents loss of MMP and inhibits the mitochondria-mediated apoptosis. These results indicate that the inhibition of Drp-1 activation by Apelin is a novel mechanism of cardioprotection against MI injury.
doi_str_mv 10.18632/oncotarget.21777
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Apelin decreased Bax/Bcl-2 ratio and limited the release of cytochrome C and activation of caspase-9 and caspase-3 both and . Finally, Apelin diminished the infarct size and normalized the impaired cardiac function as indicated by rescuing of the decreased ejection faction and fractional shortening in MI mice. In conclusion, Apelin prevented mitochondrial fission by inhibiting p-Drp1 , which prevents loss of MMP and inhibits the mitochondria-mediated apoptosis. 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Apelin decreased Bax/Bcl-2 ratio and limited the release of cytochrome C and activation of caspase-9 and caspase-3 both and . Finally, Apelin diminished the infarct size and normalized the impaired cardiac function as indicated by rescuing of the decreased ejection faction and fractional shortening in MI mice. In conclusion, Apelin prevented mitochondrial fission by inhibiting p-Drp1 , which prevents loss of MMP and inhibits the mitochondria-mediated apoptosis. 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title Apelin protects against myocardial ischemic injury by inhibiting dynamin-related protein 1
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