| Abstract: | Background Restenosis and atherosclerosis are two disorders characterized by abundant proliferation and migration of vascular smooth muscle cells(VSMCs).Previous studies have demonstrated a protective effect of the cellular repressor of E1A-stimulated genes(CREG) against restenosis. However,the role of CREG in atherosclerosis is undetermined. The aim of the present study is to examine the impact of CREG on the atherosclerosis.Methods Both immunofluorescence and western blotting were used in this experiment. Results The expression of CREG was decreased markedly in atherosclerotic lesions compared with normal areas of the vessels from both humans and mice species.We furthermore demonstrated that compared with the adenovirus-mediated-GFP control,intravenous administration of adenovirus-mediated CREG to apolipoprotein E deficient mice with six-week high-fat diet significantly reduced the relative area of atherosclerotic lesions in the mice aorta,accompanied by a decreased levels of Tumor necrosis factor(TNF) -αand Interleukin (IL)-1βmeasured by ELISA.Meanwhile,Western analysis revealed that NF-κB activation was also markedly reduced.Studies of cultured human VSMCs identified that overexpression of CREG abrogated the proliferation of human VSMCs stimulated by ox-LDL,along with a significantly decreased releasing of TNF-αand IL-1β.Conversely,down-regulation CREG expression contributed to cells proliferation stimulated by ox-LDL in cultured human VSMCs.Furthermore, overexpression of CREG suppressed the activations of NF-kB and ERK1/2 in cultured cells,while Furthermore, treatment with ERK inhibitor PD98059 reversed the CREG-mediated inhibition of human VSMCs proliferation.Conclusions CREG has a protective effect against atherosclerosis, which is related to inhibiting proliferation and inflammatory response of VSMCs. |
