Association of serum CTRP4 levels with vascular endothelial function in patients with type 2 diabetes mellitus: CTRP4 ameliorating inflammation, proliferation and migration in human umbilical vein endothelial cells.

Abstract

We investigated the correlation between serum C1q/TNF-related protein 4 (CTRP4) level and flow-mediated dilation (FMD) in patients with type 2 diabetes mellitus (T2DM), and evaluated the biological effects of CTRP4 on human umbilical vein endothelial cells (HUVECs). A group of 165 patients diagnosed with T2DM were included in this study. Endothelial function was measured with the examination of brachial artery FMD. ELISA kit was used to measure the levels of CTRP4 in serum. HUVECs were stimulated with recombinant CTRP4 protein to assess its biological functions. The levels of CTRP4 showed a significant variation among three groups based on FMD tertiles (p = 0.001). What's more, FMD had a significant difference among three CTRP4 tertile groups (p < 0.05) and was negatively related to serum CTRP4 levels (r = -0.270, p < 0.001). In T2DM patients, logistic regression analysis demonstrated that CTRP4 was the primary influence factor of low FMD (p < 0.01). In receiver operating characteristic curve analysis, the area under the curve of CTRP4 for predicting low FMD was 0.66 (95%CI 0.58-0.75). When stimulated HUVECs with recombinant CTRP4 protein, we found that CTRP4 could concentration-dependently ameliorate proliferation and migration of HUVECs in wounding healing and transwell assay. This protein could also decrease the expression of IL-6 and TNF-α and promote the release of NO in HUVEC supernatants, with suppression of NF-κB and STAT3 phosphorylation. Serum CTRP4 concentrations were negatively associated with FMD. CTRP4 alleviated proliferation, migration and inflammation in HUVECs through the suppression of NF-κB and STAT3 signaling pathways.