title: Effect of intermittent hypoxia on the cardiac HIF-1/VEGF pathway in experimental type 1 diabetes mellitus.
abstract: OBJECTIVE
  High altitude and hypoxic preconditioning have cardioprotective effects by increasing coronary vascularity, reducing post-ischemic injury, and improving cardiac function. Our purpose was to examine if intermittent hypoxia treatment has any restoring effects related to the possible role of the HIF-1/VEGF pathway on diabetic cardiomyopathy.
  
  
  METHODS
  Wistar Albino male rats (n=34) were divided into four groups: control (C), intermittent hypoxia (IH), diabetes mellitus (DM), and diabetes mellitus plus intermittent hypoxia (DM+IH). Following a streptozotocin (STZ) injection (50 mg/kg, i.p.), blood glucose levels of 250 mg/dL and above were considered as DM. IH and DM+IH groups were exposed to hypoxia 6 h/day for 42 days at a pressure corresponding to 3000 m altitude. Twenty-four hours after the IH protocol, hearts were excised. Hematoxylin and eosin-stained apical parts of the left ventricles were evaluated. Hypoxia inducible factor-1 (HIF-1), vascular endothelial growth factor 164 (VEGF164), and VEGF188 polymerase chain reaction products were run in agarose gel electrophoresis. Band density analysis of UV camera images was performed using Image J. The data were compared by one-way ANOVA, repeated measures two-way ANOVA, and the Kruskal-Wallis test.
  
  
  RESULTS
  The percent weight change was lower in the DM group than in the controls (p=0.004). The tissue injury was the highest in the DM group and the least in the IH group. Diabetes decreased, whereas the IH treatment increased the vascularity. A decrease was observed in the VEGF188 mRNA levels in the DM+IH group compared with the C group, but there were no difference in HIF-1α and VEGF164 mRNA levels between the groups.
  
  
  CONCLUSIONS
  The IH treatment restored the diabetic effects on the heart by reducing tissue injury and increasing the capillarity without transcriptional changes in HIF-1/VEGF correspondingly.
authors.affiliation: Department of Physiology, Faculty of Medicine, Sakarya University; Sakarya-Turkey. addursun@ankara.edu.tr.
authors.forename: Derya
authors.initials: D
authors.lastname: Güzel
authors.forename: Ali Doğan
authors.initials: AD
authors.lastname: Dursun
authors.forename: Hakan
authors.initials: H
authors.lastname: Fıçıcılar
authors.forename: Demet
authors.initials: D
authors.lastname: Tekin
authors.forename: Ayhan
authors.initials: A
authors.lastname: Tanyeli
authors.forename: Fırat
authors.initials: F
authors.lastname: Akat
authors.forename: Ferda
authors.initials: F
authors.lastname: Topal Çelikkan
authors.forename: Bizden
authors.initials: B
authors.lastname: Sabuncuoğlu
authors.forename: Metin
authors.initials: M
authors.lastname: Baştuğ
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D058065:Diabetic Cardiomyopathies / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D051793:Hypoxia-Inducible Factor 1 / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A