Leukocyte cell-derived chemotaxin 2 inhibits development of atherosclerosis in mice

Abstract

Leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional hepatokine, is involved in many pathological conditions. However, its role in atherosclerosis remains undefined. In this study, we administered vehicle or LECT2 to male Apoe -/- mice fed a Western diet for 15 weeks. Atherosclerotic lesions were visualized and quantified with Oil-red O and hematoxylin staining. The mRNA expression levels of MCP-1, MMP-1, IL-8, IL-1β, and TNF-α were analyzed by quantitative real-time polymerase chain reaction. Serum TNF-α, IL-1β, IL-8, MCP-1, and MMP-1 concentrations were measured by enzyme-linked immunosorbent assay. CD68, CD31, and α-SMA, markers of macrophages, endothelial cells, and smooth muscle cells, respectively, were detected by immunostaining. Results showed that LECT2 reduced total cholesterol and low-density lipoprotein concentrations in serum and inhibited the development of atherosclerotic lesions, accompanied by reductions in inflammatory cytokines and lower MCP-1, MMP-1, TNF-α, IL-8, and IL-1β mRNA abundance. Furthermore, LECT2 decreased CD68, but increased α-SMA in atherosclerotic lesions, suggesting an increase in smooth muscle cells and reduction in macrophages. In summary, LECT2 inhibited the development of atherosclerosis in mice, accompanied by reduced serum total cholesterol concentration and lower inflammatory responses.

Downregulation of LncRNA NORAD promotes Ox-LDL-induced vascular endothelial cell injury and atherosclerosis

“…IL-8 is another widely studied gene that is relevant to atherogenesis. In atherosclerosis, ox-LDL induces the overexpression of IL-8 by the vascular endothelial cells, which could activate macrophages and aggravate inflammatory responses [40]. Our study showed that NORADknockdown increased the IL-8 levels in ox-LDLtreated HUVECs.…”

Serum leukocyte cell-derived chemotaxin 2 level is associated with atopic dermatitis patients

“…Additionally, the relationships between the levels of serum LECT2 and eosinophil levels of AD patients (eosinophil In recent years, studies have been focused on the relationships between LECT2 and inflammatory diseases. (13). Furthermore, Tanisawa et al reported that participants with dyslipidemia had higher levels of plasma LECT2 than those without dyslipidemia (17).…”

“…We believe that LECT2 may cause the occurrence of AD in many ways. LECT2 is associated with many inflammation-linked signaling pathways such as NF-κB and STAT1, among others (12,13,15). NF-κB is an important transcriptional regulator that modulates the immune and inflammatory responses involved in the transcription of several targets (24).…”

“…It has been identified as a neutrophil chemotactic protein, and it participates in many physiological and pathological processes such as hepatocarcinogenesis (10), bacterial sepsis (11), and nonalcoholic fatty liver disease (NAFLD) (12). As a liverproduced and blood-secreted protein, LECT2 was also found to be associated with autoimmune and chronic inflammation conditions such as atherosclerosis (13) and chronic gastritis (14). Previous studies found that LECT2 enhanced inflammation markers such as IκB phosphorylation (15), nuclear factor kappa-B (NF-κB) phosphorylation ( 13), and IL-6 expression (12).…”

Homocysteine promotes migration of adventitial fibroblasts via Angiotensin II type 1 receptor activation to aggravate atherosclerosis

“…They were incubated in diaminobenzidine until a change in color was observed under the microscope and then the nucleus was stained with hematoxylin. 22 Immuno uorescence staining procedure was similar to immunostaining.…”