ISSN 2149-2263 | E-ISSN 2149-2271
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Intermittent hypoxia induces beneficial cardiovascular remodeling in left ventricular function of type 1 diabetic rat [Anatol J Cardiol]
Anatol J Cardiol. 2018; 19(4): 259-266 | DOI: 10.14744/AnatolJCardiol.2018.00236

Intermittent hypoxia induces beneficial cardiovascular remodeling in left ventricular function of type 1 diabetic rat

Fırat Akat1, Hakan Fıçıcılar1, Ayşegül Durak2, Erkan Tuncay2, Ali Doğan Dursun1, Ferda Topal Çelikkan3, Bizden Sabuncuoğlu3, Belma Turan2, Metin Baştuğ1
1Department of Physiology, Faculty of Medicine, Ankara University; Ankara-Turkey
2Department of Biophysics, Faculty of Medicine, Ankara University; Ankara-Turkey
3Department of Histology and Embryology, Faculty of Medicine, Ankara University; Ankara-Turkey

Objective: Depressed mechanical activity is a marked complication in diabetics. Hypoxia has properties for novel diagnostic and therapeutic strategies, while intermittent hypoxia (IH) provides early functional and histologic remodeling, including some cardio benefits in early hemodynamic alterations with histologic remodeling and delayed changes in peripheral vasoreactivity. Therefore, we aimed to examine whether IH application presents a cardioprotective effect, via stabilization of hypoxia-inducible factor (HIF) in streptozotocin (STZ)-induced diabetic rat heart.
Methods: Male 10-week-old Wistar rats were randomly assigned as control group (C), IH group, (STZ)-induced diabetic group (DM) and IH applied DM group (DM+IH). Diabetes duration was kept 6 weeks and IH groups were exposed to hypobaric hypoxia at about 70 kPa (including ~14% PO2; 6 h/day for 6-weeks).
Results: Depressed left ventricular developed pressure (LVDP) and prolonged contraction and relaxation of Langendorff-perfused hearts, as well as increased total oxidative status from streptozotocin (STZ)-induced diabetic rats were markedly prevented with IH application. IH application induced significant increase in protein expression levels of both HIF-1α and vascular endothelial growth factor (VEGF), in both control and diabetic rat hearts, whereas there were significant decreases in the protein levels of prolyl-4 hydroxylase domain enzymes, PHD2, and PHD3 in diabetic hearts. Furthermore, IH application induced marked increases in protein levels of matrix metalloproteinases, MMP-2 and MMP-9 and capillary density in left ventricle of diabetic rats.
Conclusion: Overall, we presented how IH application has a beneficial cardiovascular remodeling effect in left ventricular function of diabetic rats, at most, via affecting increased oxidative stress and HIF-VEGF related angiogenesis, providing information on hyperglycemia associated new targets and therapeutic strategies.

Keywords: diabetic cardiomyopathy, intermittent hypoxia, hypoxia-inducible factor (HIF), vascular endothelial growth factor (VEGF), angiogenesis

Fırat Akat, Hakan Fıçıcılar, Ayşegül Durak, Erkan Tuncay, Ali Doğan Dursun, Ferda Topal Çelikkan, Bizden Sabuncuoğlu, Belma Turan, Metin Baştuğ. Intermittent hypoxia induces beneficial cardiovascular remodeling in left ventricular function of type 1 diabetic rat. Anatol J Cardiol. 2018; 19(4): 259-266

Corresponding Author: Fırat Akat, Türkiye
Manuscript Language: English


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