The Korean Journal of Internal Medicine

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Korean J Med. 2006;71(1):287-287.
Resistin : A Novel Angiogenic Factor in Obesity
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Resistin : A Novel Angiogenic Factor in Obesity
, , , , ,
1Department of Internal Medicine, Hanyang University College of Medicine, Seoul; 2Department of Life Science, Postech Biotech Center, Pohang University of Science and Technology, Pohang, Korea


Abstract
Background : Obesity is a major risk factor for cardiovascular disease, diabetes, and cancer, which are all closely linked to angiogenesis. Resistin, originally discovered as a novel adipokine, has been shown to be significantly increased in obese individuals. However, the effects of resistin on endothelial cells and angiogenesis, are virtually unknown. Here, we investigated the effects of resistin on human umbilical vein endothelial cell (HUVEC) proliferation, migration, and capillary formation, in vitro, and confirmed its effect on in vivo angiogenesis in a matrigel plug assay. We also studied putative signaling pathways, by which resistin exerts these effects. Methods and Results : Resistin significantly enhanced HUVEC proliferation and migration, as measured by direct cell counting and scratch wound assay. Western blot analysis showed that resistin significantly increased the phosphorylation, and thus, activation of mainly Akt and to a lesser degree, Erk1/2, two well known pro-proliferative cell signals. This augmentation of EC proliferation and migration by resistin, led to significantly increased capillary formation as measured by Matrigel tube forming assay, which was significantly inhibited by mainly LY294002, a PI3-kinase inhibitor, and to a lesser degree, by PD98059, a MEK inhibitor. LY294002, also significantly reversed the increased migratory effects of resistin. Furthermore, we confirmed in vivo, using a matrigel plug assay, that angiogenesis was significantly enhanced by resistin, which was inhibited by blocking Akt and Erk1/2. Conclusion : Resistin enhances endothelial cell proliferation and migration, thus resulting in increased capillary tube formation through mainly activating the PI3-kinase/Akt pathway. Our findings suggest that resistin may be a novel link between obesity and atherosclerosis and cardiovascular disease, through promotion of angiogenesis.

Keywords :
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