Inhibition of triggering receptor expressed on myeloid cells-1(TREM-1) attenuates chronic intermittent hypoxia-induced atherosclerosis in mouse models

Abstract

Objective To investigate the role of triggering receptor expressed on myeloid cells-1(TREM-1) in atherosclerosis induced by chronic intermittent hypoxia (CIH). Methods ApoE-/- mice were randomly divided into blank group, model group and experimental group. The mice in the model group and the experimental group were kept in a hypoxic environment and fed with a high-fat diet. After 4 weeks of high-fat feeding, mice in the experimental group were intraperitoneally injected with TREM-1 inhibitor LR12 (5 mg/kg) for 8 weeks. After 12 weeks of feeding, the level of serum total cholesterol (TC), low density lipoprotein (LDL), triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-1β(IL-1β) and interleukin-10 (IL-10) were detected. Histological analysis of aortic TREM-1 expression, plaque area and macrophage level were examined. Results Compared with blank group, the expression of TREM-1 in the aorta of the model group significantly increased (P＜0.05). Compared with model group, the aortic plaque, the level of lipids in serum(TC, LDL, TG) and inflammatory factors (TNF-α, IL-1β, IL-10), aortic plaque, the expression of TREM-1 and infiltrating macrophages in aortic plaque of the experimental group were all significantly reduced (P＜0.05). Conclusions TREM-1 is involved in the development of CIH-induced AS. Inhibition of TREM-1 can alleviate CIH-induced AS and its mechanism is related to the inhibition of macrophage activation.

Keywords

• triggering receptor expressed on myeloid cells-1(trem-1)|chronic intermittent hypoxia|atherosclerosis|lipids in serum|macrophage