Establishment Of A Mouse Model Of Atherosclerosis Induced By TREM-1 In Sleep Apnea And Its Mechanism

Objective:A mouse model of chronic intermittent hypoxia(CIH)was constructed to investigate the effects of CIH on macrophage polarization and triggering receptor expressed on myeloid cells-1(TREM-1)during the promotion of atherosclerosis(AS).We investigated the effect of CIH on macrophage polarization and triggering receptor expressed on myeloid cells-1(TREM-1)during the promotion of atherosclerosis(AS),and explored the mechanism of TREM-1 in obstructive sleep apnea(OSA)causing AS.Method:Twenty-eight healthy male Apoe-/-mice were randomly divided into two groups with 14 mice in each group.The experiment was divided into two groups: high fat normal oxygen group(blank control group)and high fat combined with low oxygen group(CIH group).At the end of 20 weeks of modeling,the establishment of the mouse AS model was verified by vascular ultrasound,oil red O staining and HE staining.Then Enzyme Linked Immunosorbent Assay(ELISA)was used to detect the expression of serum lipids and cytokines in mice,including Total cholesterol,TC),Low-density lipoprotein cholesterol(LDL)and Triglycerides(TG),and cytokines including TNF-α,IL-6,IL-10 and VEGF.The effect of CIH on macrophage polarization in atherosclatherous plaques was analyzed by immunohistochemical staining with CD68 and CD206 antibodies after biopsies of mouse aorta.The expression of TREM-1 protein in mouse aortic plaque was detected by immunohistochemical method.Results:CIH can promote the formation of AS in mice: aortic ultrasound,oil red O staining and HE staining showed that compared with NC group,the area of aortic atherosclerotic plaque in CIH group was significantly increased(P < 0.001).CIH can promote the increase of serum lipid indexes: the levels of TC,LDL and TG in CIH group were significantly higher than those in NC group(P < 0.001).CIH can cause macrophage polarization in AS plaques: ELISA results showed that compared with NC group,the expression levels of IL-6 and TNF-α in serum of CIH group were significantly increased(P<0.01),while the expression levels of IL-10 and VEGF were significantly decreased(P<0.001).Immunohistochemical staining results indicated that CIH could induce the up-regulation of CD68 expression in M1-type macrophage-related protein compared with NC group.TREM-1 protein expression in the aorta of CIH group was up-regulated(P < 0.01).Compared with NC group,TREM-1 protein expression in aortic plaque tissue of mice in CIH group was significantly increased(P < 0.01).Conclusion:The mouse model of atherosclerosis induced by sleep apnea was established successfully.CIH aggravated AS in aorta of mice.CIH can induce M1-type polarization of macrophages in AS plaques and participate in the development of AS by increasing the expression of TREM-1.TREM-1 plays an important role in the pathogenesis and development of OSA.