The key oxygen sensing molecules, Prolyl-hydroxylase domain 1-3 enzymes (PHD1-3), regulate hypoxia-inducible factor
(HIF) under hypoxia. In the settings of cardiomyopathy and ischemia-reperfusion injury, PHD3 expression is elevated, resulting in decreased
HIF activation. The role of PHD3 in myocardial injury is poorly understood. Hence, we aimed to determine the effects of PHD3
deletion in mice on HIF-1α and other related pathways following myocardial infarction (MI). Left coronary artery (LAD) in both wild
type and prolyl hydroxylase 3 knock out (PHD3-/-) mice was ligated to induce myocardial infarction. Electrophoretic mobility shift analysis
showed significant increase in DNA-binding activity of HIF-1α in PHD3-/- mice as compared to wild type (WT) mice post MI. The
PHD3-/-MI group also showed decreased fibrosis. Seven days after MI, enhanced capillary / arteriolar density was observed compared to
WTMI group. PHD3-/- mice subjected to MI also showed improved cardiac functions (Ejection fraction and Fractional shortening), as assessed
by echocardiogram, compared to WT. Western blot analysis showed increased VEGF, Ang-1 & Bcl-2 expression in PHD3-/-MI
group. In conclusion, ablation of the PHD3 gene resulted in increased angiogenesis and cardiac function after infarction thereby offering
a potential target for pharmacological management of ischemic myocardial disease.
Keywords: Angiogenesis, myocardial infarction, Bcl-2, VEGF, HIF, prolyl hydroxylase.
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