title: Adiponectin exerts cardioprotection against ischemia/reperfusion injury partially via calreticulin mediated anti-apoptotic and anti-oxidative actions.
abstract: The underlying mechanisms of cardioprotection of adiponectin (APN) against ischemia/reperfusion (I/R) injury remain largely unknown. The present study aimed to investigate whether calreticulin (CRT) mediated APN's cardioprotection against I/R injury. We inhibited mice cardiac CRT expression via intra-myocardial injection of CRT SiRNA, performed transient LAD ligation, measured the cardiac function, apoptosis and oxidative stress to identify CRT's effects on cardioprotective actions of APN against I/R injury in vivo. LDH release and expression of CRT were measured in neonatal cardiomyocytes (NCM) subjected to simulated I/R (SI/R) and APN. CRT specific SiRNA was also utilized in vitro. CRT inhibition partially blunted cardioprotection of APN against I/R injury (evidenced by left ventricular ejection fraction and myocardial infarct size). It also blunted APN's function against I/R induced apoptosis and oxidative stress (evidenced by TUNEL positive staining and reactive oxygen species production). In addition, SI/R increased LDH release, and administration of APN attenuated SI/R-induced cell death significantly. However, neither SI/R nor APN altered CRT expression in NCM. Inhibition of CRT expression blunted cardioprotective action of APN against SI/R induced apoptotic events (evidenced by TUNEL positive staining, LDH release and Caspase 3 activity). Furthermore, CRT inhibition significantly blunted APN's anti-oxidative action (evidenced by gp91phoxexpression and superoxide generation). However, CRT inhibition did not attenuate AMPK phosphorylation by APN administration in NCM. Therefore, these novel findings strongly indicate that APN exerts cardioprotective effects against I/R injury partially via CRT mediated anti-apoptotic and anti-oxidative actions.
authors.affiliation: Department of Aerospace Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.|Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.|Department of Geriatric, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Dajun
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Aerospace Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an, 710038, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Aerospace Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Ren
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China. yiweifmmu@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.affiliation: Department of Aerospace Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China. fgao@fmmu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D037282:Calreticulin / Q000037:antagonists & inhibitors / Q000235:genetics*; D002316:Cardiotonic Agents / Q000378:metabolism / Q000627:therapeutic use; D053148:Caspase 3 / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000235:genetics; D051379:Mice; D009203:Myocardial Infarction / Q000235:genetics* / Q000628:therapy; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D013481:Superoxides / Q000378:metabolism
chemical_list: D052242:Adiponectin; D037282:Calreticulin; D002316:Cardiotonic Agents; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013481:Superoxides; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3
keywords: Adiponectin; Apoptosis; Calreticulin; Myocardial ischemia/reperfusion; Oxidative stress