ABSTRACT

Diabetic cardiomyopaty (DCMP) is described as ventricular dysfunction seen in diabetic patients which manifests itself without any coronary artery disease and hypertension. One may observe inter-sititial fibrosis, myocyte hypertrophy and contractile protein glycation in DCMP. Diastolic dysfunction is the earliest and most of the time only symptom of DCMP. Generally systolic dysfunction is a late symptom which is seen in patients who have significant diastolic dysfunction. DCMP has a very complex pathophysiology which can be indexed in many titles. We focused on HIF-VEGF-Angiogenesis axis which contains prolyl hydroxilases. In diabetes HIF response to hypoxia is blunted and it is known that this alteration is an important contributor to DCMP prognosis. Prolyl hydroxilases are enzymatic molecules (PHDs) which, uses molecular oxygen as cofactor and if oxygen is abundant they degrade HIF-α (hypoxia induced factor-α ) subunit. They have an important role in cellular oxygen homeostasis and HIF response to hypoxia. In hypoxic conditions, PHD becomes inactive that saves HIF-1α from degradation and HIF-1α unites with β subunit to form HIF-1 molecule. This phenomenon is named as “HIF stabilisation”. Stabilised HIF-1 molecule modifies lots of protein’s transcription rate in the cell. Activation of HIF’s downstream targets, lowers the energy and oxygen consumption and increases the delivery of oxygen to the cell which protects the cell from hypoxic damage. The genomic profile generated with HIF activation has cardioprotective effect in DCMP. HIF ove-rexpressing genetic models, hypoxia application, PHD inhibitors and PHD silencing methods is used to activate HIF system. There are limited number of studies in literature about the effect of diabetes on PHDs. Increment of PHD-based research in diabetes may help the production of valuable knowledge about preventive and therapeutical strategies in diabetes.

Keywords: Diabetic Cardiomyopathy, Prolyl hydroxylases, Hypoxia, HIF