title: HIF-1α signaling activation by post-ischemia treatment with astragaloside IV attenuates myocardial ischemia-reperfusion injury.
abstract: In this study, we evaluated the effect of astragaloside IV (Ast IV) post-ischemia treatment on myocardial ischemia-reperfusion (IR) injury (IRI). We also examined whether hypoxia inducible factor-1α (HIF-1α) and its downstream gene-inducible nitric oxide (NO) synthase (iNOS) play roles in the cardioprotective effect of Ast IV. Cultured cardiomyocytes and perfused isolated rat hearts were exposed to Ast IV during reperfusion in the presence or absence of the HIF-1α inhibitor 2-methoxyestradiol (2-MeOE2). The post-ischemia treatment with Ast IV protected cardiomyocytes from the apoptosis and death induced by simulated IRI (SIRI). Additionally, in cardiomyocytes, 2-MeOE2 and HIF-1α siRNA treatment each not only abolished the anti-apoptotic effect of post-ischemia treatment with Ast IV but also reversed the upregulation of HIF-1α and iNOS expression. Furthermore, after treatment with Ast IV, post-ischemic cardiac functional recovery and lactate dehydrogenase (LDH) release in the coronary flow (CF) were improved, and the myocardial infarct size was decreased. Moreover, the number of apoptotic cells was reduced, and the upregulation of the anti-apoptotic protein Bcl2 and downregulation of the pro-apoptotic protein Caspase3 were reversed. 2-MeOE2 reversed these effects of Ast IV on IR-injured hearts. These results suggest that post-ischemia treatment with Ast IV can attenuate IRI by upregulating HIF-1α expression, which transmits a survival signal to the myocardium.
authors.affiliation: Department of Traditional Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an City, Shaanxi Province, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Si
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an City, Shaanxi Province, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Tangdu Hospital, The Fourth Military Medical University, Xi'an City, Shaanxi Province, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an City, Shaanxi Province, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an City, Shaanxi Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Nephropathy and Immunology, BaYi Childrens Hospital of The General Military Hospital of Beijing PLA, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yi
authors.affiliation: Department of Traditional Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an City, Shaanxi Province, China.
authors.forename: Zixuan
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Traditional Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an City, Shaanxi Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Traditional Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an City, Shaanxi Province, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an City, Shaanxi Province, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an City, Shaanxi Province, China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Traditional Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an City, Shaanxi Province, China.
authors.forename: Junchang
authors.initials: J
authors.lastname: Li
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D015854:Up-Regulation
chemical_list: D004365:Drugs, Chinese Herbal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D004958:Estradiol; D000077584:2-Methoxyestradiol; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3