Circulating Levels of CILP2 Are Elevated in Coronary Heart Disease and Associated with Atherosclerosis

Abstract

Background and Objectives. Genome-wide association studies (GWAS) have shown that cartilage intermediate layer protein 2 (CILP2) is associated with blood lipid levels and coronary heart disease (CHD). However, no study has reported whether CILP2 is related to atherosclerosis in humans. The purpose of the current study is to identify the associations between CILP2 and atherosclerosis in vitro and in vivo. Methods and Results. Circulating CILP2 levels (measured by ELISA) were compared to various insulin resistance- and atherosclerosis-related parameters in normal subjects and newly diagnosed CHD patients. THP-1 cells were cultured and treated with indicated stimulators. Western blots and RT-PCR were performed to examine protein and mRNA expressions. The results showed that there were significantly higher circulating CILP2 levels in CHD patients relative to healthy controls. Circulating CILP2 correlated positively with waist-hip ratio (WHR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HbA1c, homeostasis model assessment of insulin resistance (HOMA-IR), and Gensini scores. In an in vitro study, we found that CILP2 increased oxidatively modified LDL-stimulated lipid accumulation in THP-1 macrophages via the upregulation of CD36 expression. Inhibition of PPARγ signaling eliminated the CILP2 regulation of CD36 expression in THP-1 macrophages. CILP2 positively regulated CD36 transcription through PPARγ-mediated action on two peroxisome-proliferator-responsive elements (PPREs) binding sites of CD36 promoter, PPRE-G, and PPRE-J. Conclusions. Our findings have uncovered a novel role for CILP2 in lipid uptake and foam cell formation. This role is mediated by CD36 through the activation of PPARγ pathway.

Endothelial cells regulated by RNF20 orchestrate the proliferation and differentiation of neural precursor cells during embryonic development

“…Article ll OPEN ACCESS CILP2 is a secreted protein that is associated with high-density lipoprotein cholesterol (HDL-C), but its function in embryonic brain development is unknown (Hu et al, 2020). Our research showed that CILP2 could interact with Wnt3a, which is a ligand that activates the canonical Wnt signaling pathway.…”

“…We noticed that the expression of CILP2, a secreted protein, was downregulated to the greatest extent, which was consistent with the results of qPCR (Figure 6F). Previous studies have found that CILP2 exists in the circulating blood and plays a vital role in the normal func-tion of blood vessels (Hu et al, 2020;Wu et al, 2019), but its potential function in brain development has not yet been reported. We found that CILP2 was widely expressed in ECs, which was similar to RNF20 (Figure S6A).…”

CILP2: A prognostic biomarker associated with immune infiltration in colorectal cancer

“…CILP2 is a secreted glycoprotein [ 16 ]. CILP2 was confirmed to be associated with atherosclerosis, according to Hu et al (2020), who revealed that CILP2 regulates the transcription of CD36 through the peroxisome proliferator-activated receptor gamma (PPARγ) pathway, thereby increasing the uptake of lipids by cells and resulting in atherosclerosis [ 17 ]. Luo et al (2017) reported that the rs16996148 genetic locus in CILP2 strongly influenced the risk of dyslipidemia in the Chinese population [ 18 ].…”

MicroRNA-29 Differentially Mediates Preeclampsia-Dysregulated Cellular Responses to Cytokines in Female and Male Fetal Endothelial Cells

“…However, these five DE genes had opposite regulation directions in F and M HUVECs: all were down-regulated in F but up-regulated in M HUVECs from PE. These DE genes include Activity Regulated Cytoskeleton Associated Protein (ARC) and Cartilage Intermediate Layer Protein 2 (CLIP2), both of which are important for intercellular microRNA transportation via extracellular exosome(Pastuzyn et al ., 2018; Hu et al ., 2020). Thus, fetal sex-specific dysregulation of these intercellular microRNA transportation-related genes may contribute to PE-dysregulated miR-29a/c-3p in HUVECs and fetoplacental tissues.…”