Molecular pathological studies on physiological function of VEGF in atherosclerotic Vessels

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The endothelial function, including the activation and regulation of both procoagulant and anticoagulant properties, has been considered to play a critical role in pathophysiology of blood vessel. To clarify the patho-biological function of endothelial cells, we developed new technique (ex vivo procoagulant activity assay method and HVJ-cationic liposome gene transfer technique) or new animal model (CA-LPS DIC model, etc.) and we performed histochemical, cell biological or genetical analyzes in vivo and in vitro.We revealed that atherosclerotic vessel tended to be a hypercoagulantstate and that vascular endothelial growth factor (VEGF) promoted the intimal thickness and angiogenesis in rabbit atherosclerotic model. We also demonstrated that VEGF play a central role in the modulation of endothelial cell function, especially neovascularization and hyperpermeability of blood vessels in diabetic retinopathy and placental development. Moreover, we examined the availability of antithrombotic agent, a recombinant tissue factor pathway inhibitor in thrombosis model.These results and techniques may provide a new insight for more comprehensive on endothelial function in vessel walls as well as therapeutic implications in vascular diseases.