Overexpression of SHP-1 mediated by lentivirus restrains atherosclerotic progression in mice

AIM: To investigate the role of SH2-domain-containing protein-tyrosine phosphatase-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 target for prevention and treatment of atherosclerosis.