Regy Regulate Vascular Remodeling, Arteriosclerosis And Its Mechanism Exploration

REGy protein as a kind of 11s proteasome activators, can activate the 20s proteasome to degrade some important proteins, such as SRC-3, p21, p16, p19, CK1, SIRT1, PKA which regulate tumor, aging, lipid metabolism, and angiogenesis pathway,so REGgamma plays a very important role in the process of tumor development, aging, autophagy, vascular disease etc pathological phenomenon. The function of REGgamma are being explored and broadened. Base on the existing foundation of REG gamma function research, and combining with the new hypothesis and phenomenon, REG gamma may also play a very important role in the development of vascular remodeling and atherosclerosis.This article focus on exploring the molecular mechanism, cell-based function in vitro, mice model pathological biology in vivo of REGgamma regulate vascular remodeling and atherosclerosis.We found the phenomenon that REGgamma promote the mRNA and protein expression of cyclophlin A (CypA) which plays a regulatory role in vascular remodeling and atherosclerosis,this regulation is mediated by the cAMP signaling pathway REGgama-PKA-Foxol that REGgama regulated. REG gamma through activating 20s proteasome,degrade PKACa directly, then decreases the phosphorylation and nuclear export of transcription facto Foxo1, thus promotes Foxol enter into nuclear, enhance its transcriptional activity,Foxol can binding to the CypA gene promoter as its transcriptional factor,to promote its expression, REGgama through this pathway promote CypA mRNA and protein expression.Further cell-based functional experiment in vitro found that REGgamma depend on regulating CypA to promote the vascular endothelial cell(human umbilical vein endothelial cells HUVEC) migration and chemotaxis at the VEGF stimulation, at the same time, we choose the classic vascular remodeling and atherosclerosis ApoE knockout mice as research model, ApoE knockout mice model are being bred for cross to get specific research model, comparing REG gamma regulation on arterial lipid deposition, lesion and structure morphology, to clarify and strengthen the biology in vivo further. These results provide more new ideas for the treatment of atherosclerosis.