title: Intravenous high mobility group box 1 upregulates the expression of HIF-1α in the myocardium via a protein kinase B-dependent pathway in rats following acute myocardial ischemia.
abstract: The effects of intravenous high mobility group box 1 (HMGB1) on myocardial ischemia/reperfusion (I/R) injury remains to be elucidated. The purpose of the present study was to investigate the effects of intravenous HMGB1 on the expression of hypoxia inducible factor-1α (HIF-1α) in the myocardium of rats following acute myocardial ischemia, and to examine the effects of intravenous HMGB1 on myocardial I/R injury. Male Wistar rats were divided into the following groups: Sham operation group (n=10), a group exposed to ischemia for 30 min and reperfusion for 4 h (I/R group) as a control (n=10), an HMGB group, in which 100 ng/kg HMGB was administered intravenously 30 min prior to ischemia (n=10), an LY group, in which LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), was administered intravenously (0.3 mg/kg) 40 min prior to ischemia (n=10), and the HMGB1+LY group, in which HMGB1 (100 ng/kg) and LY294002 (0.3 mg/kg) were administered intravenously 30 min and 40 min prior to ischemia, respectively (n=10). The serum levels of cardiac troponin I (cTnI) and tumor necrosis factor-α (TNF-α), and myocardial infarct size were measured. The expression levels of phosphorylated Akt and HIF-1α were investigated using western blot analyses. The results showed that pre-treatment with HMGB1 significantly decreased serum levels of cTnI, and TNF-α, and reduced myocardial infarct size following 4 h reperfusion (all P<0.05). HMGB1 also increased the expression levels of HIF-1α and p-Akt induced by I/R (P<0.05). LY294002 was found to eliminate the effects of intravenous HMGB1 on myocardial I/R injury (P<0.05). These results suggest that intravenous pre-treatment with HMGB1 may exert its cardioprotective effects via the upregulation of the myocardial expression of HIF-1α, which may be regulated by the PI3K/Akt signaling pathway, in rats following acute myocardial I/R.
authors.affiliation: Department of Cardiology, Qilu Hospital of Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: Heng-Chen
authors.initials: HC
authors.lastname: Yao
authors.affiliation: Department of Cardiology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Lan-Hua
authors.initials: LH
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng, Shandong 252000, P.R. China.
authors.forename: De-Yong
authors.initials: DY
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Qian-Feng
authors.initials: QF
authors.lastname: Han
authors.affiliation: Department of Cardiology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: Ke-Li
authors.initials: KL
authors.lastname: Tian
authors.affiliation: Department of Cardiology, Qilu Hospital of Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002867:Chromones / Q000008:administration & dosage; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D009025:Morpholines / Q000008:administration & dosage; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D019210:Troponin I / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D002867:Chromones; D024243:HMGB1 Protein; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009025:Morpholines; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D019210:Troponin I; D014409:Tumor Necrosis Factor-alpha; C104200:Hbp1 protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one