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

Özet

Objective: Depressed mechanical activity is a marked complication in diabetics. Hypoxia has properties for novel diagnostic and therapeuticstrategies, while intermittent hypoxia (IH) provides early functional and histologic remodeling, including some cardio benefits in early hemodynamicalterations with histologic remodeling and delayed changes in peripheral vasoreactivity. Therefore, we aimed to examine whether IH applicationpresents 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 appliedDM 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, aswell as increased total oxidative status from streptozotocin (STZ)-induced diabetic rats were markedly prevented with IH application. IH applicationinduced significant increase in protein expression levels of both HIF-1α and vascular endothelial growth factor (VEGF), in both control anddiabetic rat hearts, whereas there were significant decreases in the protein levels of prolyl-4 hydroxylase domain enzymes, PHD2, and PHD3 indiabetic hearts. Furthermore, IH application induced marked increases in protein levels of matrix metalloproteinases, MMP-2 and MMP-9 andcapillary 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 diabeticrats, at most, via affecting increased oxidative stress and HIF-VEGF related angiogenesis, providing information on hyperglycemia associatednew targets and therapeutic strategies.