YKL-40 promotes the progress of atherosclerosis independent of lipid metabolism in apolipoprotein E-/- mice fed a high-fat diet.

YKL-40 is recently regarded as a pro-inflammatory cytokine involved in the pathological process of atherosclerosis and lipid metabolism. However, whether YKL-40 can directly influence the development of atherosclerosis and levels of lipid parameters is unknown. The aim of this study is to explore the effects of YKL-40 on atherosclerotic features, the levels of serum lipids, and biomarkers in apolipoprotein (E)-deficient (ApoE-/-) mice fed a high-fat diet. ApoE-/- mice were injected with a recombinant adenovirus expressing mouse YKL-40 or control adenovirus through the caudal vein. The levels of serum YKL-40, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), matrix metalloproteinase-9 (MMP-9), and soluble vascular cell-adhesion molecule 1 (sVCAM-1) were measured by ELISA. Lipid metabolism parameters were measured using immunoturbidimetric assay. The size of plaque area in aorta was evaluated by Oil Red O and hematoxylin/eosin (HE) staining. The content of collagen fibers was stained with Masson, and the content of macrophages and smooth muscle cells (SMCs) in atherosclerotic lesions was investigated by immunohistochemistry. The serum levels of total cholesterol and triglycerides were similar between these two groups. Compared with the control, the levels of serum YKL-40, IL-6, TNF-alpha, MMP-9, plaque size, and macrophages in plaques were significantly increased in mice with adenovirus overexpressing YKL-40. However, the content of collagen fibers and SMCs was remarkably decreased in mice with adenovirus overexpressing YKL-40 than that in control. YKL-40 prompts the progress of atherosclerosis maybe involved with its role of pro-inflammation, but does not affect lipid metabolism in ApoE-/- mice fed a high-fat diet.