Venous endothelial cell inflammation and prevention after arterial flow transition

  • 方 少禹

Student thesis: Master's Thesis

Abstract

Little is known about the interrelations among the pathological progression of abnormal flow-induced endothelial damage and inflammatory response in vein graft disease Recently we discovered that venous-arterial transition induced the damage of venous endothelial cells (ECs) via excessive autophagy and inflammation Previous studies show that microRNAs (miRs) play an important role in modulating ECs functions The aim of our study is to investigate the detailed mechanisms of inflammatory response and potential prevention for pathological progression of vein graft disease To mimic the vein graft disease induced by mechanical overload we use the arterial laminar shear stress (ALS) to elicit inflammatory responses in venous ECs We discovered that ROS and COX-2/ NFκB both involved in the ALS-induced venous inflammation We found decrease of miR-4488 in venous ECs after ALS stimulation To establish therapeutic treatment the ROS and NFκB inhibitors were used to suppress the ALS-induced inflammation in venous EC However both ROS and NFκB inhibition could not rescue the inflammatory response Since the COX-2 induction was observed in both ex vivo and in vitro experiments the specific COX-2 inhibitor (SC-236) combined with L-arginine (L-Arg) was used to block the ALS-induced inflammatory response The pretreatment of venous ECs with combined treatment prior to the ALS stimulation provides a successful therapeutic strategy to inhibit the inflammation and venous ECs damage The miR-4488 was found to involve in the protective effect of combined treatment This study provides novel knowledge for the detailed mechanism of inflammation in venous endothelial damage resulting from flow transition and the combination of SC-236 and L-Arg may provide protective effect on vein graft from pathological changes
Date of Award2018 Jan 23
Original languageEnglish
SupervisorChia-Ching Wu (Supervisor)

Cite this

Venous endothelial cell inflammation and prevention after arterial flow transition
少禹, 方. (Author). 2018 Jan 23

Student thesis: Master's Thesis