Overexpression of SHP-1 mediated by lentivirus restrains atherosclerotic progression in mice
10.3969/j.issn.1000-4718.2015.08.008
- VernacularTitle:慢病毒介导的 SH P－1过表达抑制模型小鼠动脉粥样硬化
- Author:
Bingbing ZHANG
;
Hengliang SONG
;
Tao SUN
;
Daguo WAN
- Publication Type:Journal Article
- Keywords:
SH2-domain-containingprotein-tyrosinephosphatase-1;
Atherosclerosis;
Lentivirus;
ApoEknock-out mice
- From:
Chinese Journal of Pathophysiology
2015;(8):1395-1400
- CountryChina
- Language:Chinese
-
Abstract:
AIM:ToinvestigatetheroleofSH2-domain-containingprotein-tyrosinephosphatase-1(SHP-1) lentivirus in atherosclerotic mice .METHODS:ApoE knock-out mice were randomly assigned to 3 groups:control group , GFP transfection group and SHP-1 transfection group .All mice were placed with carotid collars on the right common carotid arteries near its bifurcation , following feeding with high-fat diet for 8 weeks and then transfected with GFP blank vector or SHP-1 lentivirus ( SHP-1-LV) .The fluorescence density of the plaques , body weight , the levels of plasma total cholesterol (TC) and triglyceride (TG) were determined at 1st, 2nd, and 6th week after lentivirus transfection.Furthermore, the mRNA and protein expression of SHP-1, interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), matrix metalloproteinase ( MMP)-2 and MMP-9 were analyzed by real-time PCR and Western blot .Additionally , pathological analysis of the plaques was also performed by HE and oil red O staining .RESULTS:The fluorescence of the plaques was observed at 1st, 2nd, and 6th week after lentivirus transfection , with a highest density at 2nd week.The body weight and the levels of TC and TG in the mice were not influenced by lentivirus transfection .Moreover, SHP-1-LV transfection significantly upregulated the expression of SHP-1 at mRNA and protein levels, but inhibited the expression of IL-6, TNF-α, MMP-2 and MMP-9.In addition, SHP-1-LV transfection also decreased the plaque size ratio and lipid content in right common carotid arteries . CONCLUSION:SHP-1 overexpression accelerates the regression of atherosclerotic plaque , thus emerging SHP-1 as a tar-get for prevention and treatment of atherosclerosis .
