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Publication : Inhibition of siglec-1 by lentivirus mediated small interfering RNA attenuates atherogenesis in apoE-deficient mice.

First Author  Xiong YS Year  2017
Journal  Clin Immunol Volume  174
Pages  32-40 PubMed ID  27871915
Mgi Jnum  J:318409 Mgi Id  MGI:6859548
Doi  10.1016/j.clim.2016.11.005 Citation  Xiong YS, et al. (2017) Inhibition of siglec-1 by lentivirus mediated small interfering RNA attenuates atherogenesis in apoE-deficient mice. Clin Immunol 174:32-40
abstractText  BACKGROUND: Siglec-1 is highly expressed on circulating monocytes and plaque macrophages in atherosclerotic patients, but the exact role of Siglec-1 in atherosclerosis has not been elucidated. METHODS: Lentiviral vector containing small interfering RNA targeting Siglec-1 (Lv-shSiglec-1) or control vector (Lv-shNC) were injected intravenously into 6-week old Apoe(-/-) mice. Then onset of atherosclerosis was observed. RESULTS: Siglec-1 was highly expressed in aortic plaques and it can be down-regulated by Lv-shSiglec-1 injection. The plaque area and serum pro-inflammatory cytokine (IL-1beta, IL-6, TNF-alpha and IL-17A) levels in Lv-shSiglec-1 mice were significantly lower than Lv-shNC mice, whereas IL-10 was higher. Moreover, plaque macrophages accumulation in aortic wall in Lv-shSiglec-1 mice was diminish, partly by decreased secretion of MCP-1/CXCL2 and CCR2/CXCR2 of aortas and monocytes, respectively. Furthermore, silencing of Siglec-1 can attenuate oxLDL uptake by peritoneal macrophages. CONCLUSIONS: Inhibition of Siglec-1 can prevent atherosclerotic lesion formation by suppress monocytes-endothelial cells adhesion and macrophages accumulation.
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