Mechanism for angiogenic effect of leptin

OBJECTIVE:To investigate the potential role of leptin as a angiogenic factor and whether the angiogenic effect is related to the hypoxia-inducible factor 1-mediated VEGF expression.METHODS:The expression level of HIF-1α and VEGF protein and mRNA were also assayed by western blotting and semiquantitative RT-PCR.RESULTS:Leptin at the concentration of 10 ng/mL caused a significant increase in DNA synthesis in HUVECs 〔OD(0.572±0.027)vs(0.284±0.031)in control group(P0.05)〕.The incubation with leptin led to a significantly augmented migratory rate 〔(21.1±0.32)% vs(9.99±0.43)% in control group(P0.05)〕.Leptin(100 ng/mL)induced the differentiation of endothelial cells into capillary-like structures 〔(5.8±0.5)mm vs 0 mm in control group(P0.05)〕.In addition,Western blot analysis revealed that the incubation of HUVECs with leptin resulted in a concentration-dependent elevation of HIF-1α protein and VEGF protein expressions(1 μg/mL to the max),witch induced by the enhanced expression of HIF-1α mRNA and VEGF mRNA expression respectively.CoCl2 had no effect on the expression of HIF-1α mRNA in control group.CONCLUSIONS:Leptin exerts an angiogenic effect on HUVECs by stimulating proliferation,migration and the in vitro vasculogenesis ability.Leptin increases HIF-1α protein and consequently enhances the VEGF mRNA level via the effects on the translation machinery.