Effect of intermittent hypoxia on the cardiac HIF-1/VEGF pathway in experimental type 1 diabetes mellitusDerya Güzel1, Ali Doğan Dursun2, Hakan Fıçıcılar2, Demet Tekin2, Ayhan Tanyeli4, Fırat Akat2, Ferda Topal Çelikkan3, Bizden Sabuncuoğlu3, Metin Baştuğ2
1Department Of Physiology, Faculty Of Medicine, Sakarya University; Sakarya- Turkey
2Department Of Physiology, Faculty Of Medicine, Ankara University; Ankara- Turkey
3Histology And Embryology, Faculty Of Medicine, Ankara University; Ankara- Turkey
4Department Of Physiology, Faculty Of Medicine, Atatürk University; Erzurum- Turkey
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.Keywords: angiogenesis, diabetic cardiomyopathy, intermittent hypoxia, HIF-1, VEGF
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.
Conclusion: 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.
Derya Güzel, Ali Doğan Dursun, Hakan Fıçıcılar, Demet Tekin, Ayhan Tanyeli, Fırat Akat, Ferda Topal Çelikkan, Bizden Sabuncuoğlu, Metin Baştuğ. Effect of intermittent hypoxia on the cardiac HIF-1/VEGF pathway in experimental type 1 diabetes mellitus. Anatol J Cardiol. 2016; 16(2): 76-83
Sorumlu Yazar: Ali Doğan Dursun, Türkiye