CTRP3 Protects against High Glucose-Induced Cell Injury in Human Umbilical Vein Endothelial Cells.

Yingguang Shan,Fang Wang,Ran Li,Linlin Zhao,Guijun Qin

doi:10.1155/2019/7405602

Abstract

Aims Inflammation was closely associated with diabetes-related endothelial dysfunction. C1q/tumor necrosis factor-related protein 3 (CTRP3) is a member of the CTRP family and can provide cardioprotection in many cardiovascular diseases via suppressing the production of inflammatory factors. However, the role of CTRP3 in high glucose- (HG-) related endothelial dysfunction remains unclear. This study evaluates the effects of CTRP3 on HG-induced cell inflammation and apoptosis. Materials and Methods To prevent high glucose-induced cell injury, human umbilical vein endothelial cells (HUVECs) were pretreated with recombinant CTRP3 for 1 hour followed by normal glucose (5.5 mmol/l) or high glucose (33 mmol/l) treatment. After that, cell apoptosis and inflammatory factors were determined. Results Our results demonstrated that CTRP3 mRNA and protein expression were significantly decreased after HG exposure in HUVECs. Recombinant human CTRP3 inhibited HG-induced accumulation of inflammatory factors and cell loss in HUVECs. CTRP3 treatment also increased the phosphorylation levels of protein kinase B (AKT/PKB) and the mammalian target of rapamycin (mTOR) in HUVECs. CTRP3 lost its inhibitory effects on HG-induced cell inflammation and apoptosis after AKT inhibition. Knockdown of endogenous CTRP3 in HUVECs resulted in increased inflammation and decreased cell viability in vitro. Conclusions Taken together, these findings indicated that CTRP3 treatment blocked the accumulation of inflammatory factors and cell loss in HUVECs after HG exposure through the activation of AKT-mTOR signaling pathway. Thus, CTRP3 may be a potential therapeutic drug for the prevention of diabetes-related endothelial dysfunction.

Highlights

Hyperglycemia is one of the major causes of vascular complications in patients with diabetes [1, 2]
We found that C1q/tumor necrosis factor-related protein 3 (CTRP3) was downregulated in human umbilical vein endothelial cells (HUVECs) after high glucose treatment and that CTRP3 administration reduced high glucose-induced cell inflammation and cell death via activating the protein kinase B (AKT/PKB) signaling pathway
Our results demonstrated that CTRP3 mRNA and protein expression were significantly decreased in high glucose- (HG-)treated HUVECs

Summary

Introduction

Hyperglycemia is one of the major causes of vascular complications in patients with diabetes [1, 2]. Diabetes-related endothelial dysfunction contributed to the development of diabetic vascular complications [3]. Sustained high glucose (HG) induced profound production of inflammatory factors in endothelial cells, resulting in the death of the endothelium and apoptosis [5, 6]. To prevent diabetes-related endothelial dysfunction, it is imperative to find molecules that could inhibit HG-induced inflammation and cell apoptosis. Ma et al found that CTRP3 improved cardiac dysfunction and prevented diabetes-related cardiac injury in rats [9]. We conducted the present study to explore the potential effects of CTRP3 on diabetes-related endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). We found that CTRP3 was downregulated in HUVECs after high glucose treatment and that CTRP3 administration reduced high glucose-induced cell inflammation and cell death via activating the protein kinase B (AKT/PKB) signaling pathway

Methods and Materials

Result

Discussion