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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 |
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creator | Xu, Wei Yu, Hongwei Ma, Ruixue Ma, Lina Liu, Qiushuang Shan, Huitong Wu, Chengyu Zhang, Rong Zhou, Yuhong Shan, Hongli |
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 |
format | article |
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) 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.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.21777</identifier><identifier>PMID: 29245958</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Research Paper</subject><ispartof>Oncotarget, 2017-11, Vol.8 (59), p.100034-100044</ispartof><rights>Copyright: © 2017 Xu et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-da02ad0f933cc5fb9bb8379883628ce451d4dd487c34750558882283db1330133</citedby><cites>FETCH-LOGICAL-c399t-da02ad0f933cc5fb9bb8379883628ce451d4dd487c34750558882283db1330133</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725000/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725000/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29245958$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Yu, Hongwei</creatorcontrib><creatorcontrib>Ma, Ruixue</creatorcontrib><creatorcontrib>Ma, Lina</creatorcontrib><creatorcontrib>Liu, Qiushuang</creatorcontrib><creatorcontrib>Shan, Huitong</creatorcontrib><creatorcontrib>Wu, Chengyu</creatorcontrib><creatorcontrib>Zhang, Rong</creatorcontrib><creatorcontrib>Zhou, Yuhong</creatorcontrib><creatorcontrib>Shan, Hongli</creatorcontrib><title>Apelin protects against myocardial ischemic injury by inhibiting dynamin-related protein 1</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><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.</description><subject>Research Paper</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNpVkU1rAyEQhqW0NCXND-il7LGXTVdds3ophNAvCPTSXnoRV83GsKupuoX995UkTVNh8IWZeUbnBeAGFlNIZxjdOytdFL7RcYpgVVVn4AqykuWIEHx-okdgEsKmSIeUFUXsEowQQyVhhF6Bz_lWt8ZmW--iljFkohHGhph1g5PCKyPazAS51p2RmbGb3g9ZPSS1NrWJxjaZGqzojM29bkXUak9KRHgNLlaiDXpyuMfg4-nxffGSL9-eXxfzZS4xYzFXokBCFSuGsZRkVbO6prhilOIZolKXBKpSqZJWEpcVKQihlCJEsaohxkWKMXjYc7d93WkltY1etHzrTSf8wJ0w_H_GmjVv3DcnFSJpKwlwdwB499XrEHmXvqzbVljt-sAhS9ulCEOUSuG-VHoXgter4xhY8J0t_M8WvrMl9dyevu_Y8WsC_gFshY1d</recordid><startdate>20171121</startdate><enddate>20171121</enddate><creator>Xu, Wei</creator><creator>Yu, Hongwei</creator><creator>Ma, Ruixue</creator><creator>Ma, Lina</creator><creator>Liu, Qiushuang</creator><creator>Shan, Huitong</creator><creator>Wu, Chengyu</creator><creator>Zhang, Rong</creator><creator>Zhou, Yuhong</creator><creator>Shan, Hongli</creator><general>Impact Journals LLC</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20171121</creationdate><title>Apelin protects against myocardial ischemic injury by inhibiting dynamin-related protein 1</title><author>Xu, Wei ; Yu, Hongwei ; Ma, Ruixue ; Ma, Lina ; Liu, Qiushuang ; Shan, Huitong ; Wu, Chengyu ; Zhang, Rong ; Zhou, Yuhong ; Shan, Hongli</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-da02ad0f933cc5fb9bb8379883628ce451d4dd487c34750558882283db1330133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Research Paper</topic><toplevel>online_resources</toplevel><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Yu, Hongwei</creatorcontrib><creatorcontrib>Ma, Ruixue</creatorcontrib><creatorcontrib>Ma, Lina</creatorcontrib><creatorcontrib>Liu, Qiushuang</creatorcontrib><creatorcontrib>Shan, Huitong</creatorcontrib><creatorcontrib>Wu, Chengyu</creatorcontrib><creatorcontrib>Zhang, Rong</creatorcontrib><creatorcontrib>Zhou, Yuhong</creatorcontrib><creatorcontrib>Shan, Hongli</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Wei</au><au>Yu, Hongwei</au><au>Ma, Ruixue</au><au>Ma, Lina</au><au>Liu, Qiushuang</au><au>Shan, Huitong</au><au>Wu, Chengyu</au><au>Zhang, Rong</au><au>Zhou, Yuhong</au><au>Shan, Hongli</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Apelin protects against myocardial ischemic injury by inhibiting dynamin-related protein 1</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-11-21</date><risdate>2017</risdate><volume>8</volume><issue>59</issue><spage>100034</spage><epage>100044</epage><pages>100034-100044</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>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.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>29245958</pmid><doi>10.18632/oncotarget.21777</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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title | Apelin protects against myocardial ischemic injury by inhibiting dynamin-related protein 1 |
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