유동전단응력에 의한 혈관신생의 조절

Abstract

Angiogenesis is a crucial process in physiological and pathological conditions such as embryogenesis, wound healing and tumor vascularization. The formation of blood vessel is modulated by biochemical factors as well as mechanical stimuli. Since endothelial cells are continuously exposed to fluid shear stress due to blood flow, shear stress plays essential roles in regulating angiogenesis. We are determining the effects of fluid shear stress on the endothelial cell invasion into 3D matrix. Microfludic platform was developed to apply controlled fluid shear stress to the cells plated on collagen gel, maintaining vascular endothelial growth factor (VEGF) gradient. Our hypothesis is that physiological level of fluid shear stress makes cells sensitive to initiate S1P-induced endothelial invasion. Moreover VEGF gradient can synergistically enhance their directional migration into 3D matrix. Shear-modulated angiogenesis can be explained by upregulation of Akt pathway and proteolytic activity.