title: TIR/BB-loop mimetic AS-1 attenuates cardiac ischemia/reperfusion injury via a caveolae and caveolin-3-dependent mechanism.
abstract: AS-1, the TIR/BB loop mimetic, plays a protective role in cardiac ischemia/reperfusion (I/R) but the molecular mechanism remains unclear. The muscle specific caveolin3 (Cav-3) and the caveolae have been found to be critical for cardioprotection. This study aimed to evaluate our hypothesis that caveolae and Cav-3 are essential for AS-1-induced cardioprotection against myocardial I/R injury. To address these issues, we analyzed the involvement of Cav-3 in AS-1 mediated cardioprotection both in vivo and in vitro. We demonstrate that AS-1 administration significantly decreased infarct size, improved cardiac function after myocardial I/R and modulated membrane caveolae and Cav-3 expression in the myocardium. For in vitro studies, AS-1 treatment prevented Cav-3 re-distribution induced by H/R injury. In contrast, disruption of caveolae by MCD treatment or Cav-3 knockdown abolished the protection against H/R-induced myocytes injury by AS-1. Our findings reveal that AS-1 attenuates myocardial I/R injury through caveolae and Cav-3 dependent mechanism.
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, 818 Tianyuan Dong Road, Nanjing 211166, Jiangsu, China.|Department of Pharmacy, The Binhu Hospital of Hefei, Hefei, Anhui, China.|Department of Pharmacy, The Binhu Hospital of Hefei, Hefei, Anhui, China; The First People Hospital of Hefei, Hefei, 230001, Anhui, China.
authors.forename: Yuanping
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, 818 Tianyuan Dong Road, Nanjing 211166, Jiangsu, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, 818 Tianyuan Dong Road, Nanjing 211166, Jiangsu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Shen
authors.affiliation: Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Dai
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, 818 Tianyuan Dong Road, Nanjing 211166, Jiangsu, China.
authors.forename: Danyang
authors.initials: D
authors.lastname: Ren
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, 818 Tianyuan Dong Road, Nanjing 211166, Jiangsu, China.
authors.forename: Linli
authors.initials: L
authors.lastname: Que
authors.affiliation: Department of Surgery, East Tennessee State University, Campus Box 70575, Johnson City, TN 37614-0575, USA.
authors.forename: Tuanzhu
authors.initials: T
authors.lastname: Ha
authors.affiliation: Department of Surgery, East Tennessee State University, Campus Box 70575, Johnson City, TN 37614-0575, USA.
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, 818 Tianyuan Dong Road, Nanjing 211166, Jiangsu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, China.
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Ju
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, 818 Tianyuan Dong Road, Nanjing 211166, Jiangsu, China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002316:Cardiotonic Agents / Q000494:pharmacology*; D021941:Caveolae / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051244:Caveolin 3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004452:Echocardiography; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D057786:Peptidomimetics / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; C495548:Cav3 protein, mouse; D051244:Caveolin 3; D057786:Peptidomimetics; D034741:RNA, Small Interfering