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

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-1β, IL-6, TNF-α 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.