Liraglutide promotes the angiogenic ability of human umbilical vein endothelial cells through the JAK2/STAT3 signaling pathway

• Published in: Biochemical and biophysical research communications Vol. 523; no. 3; pp. 666 - 671
• Main Authors: Di, Yanbo, He, Jing, Ma, Ping, Shen, Na, Niu, Chunhong, Liu, Xuan, Du, Xiaoming, Tian, Fengshi, Li, Huanming, Liu, Yong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.03.2020
• Subjects: Angiogenesis; HUVECs; JAK2/STAT3; Liraglutide; Angiogenesis; JAK2/STAT3; Liraglutide; HUVECs
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.01.004

Liraglutide is a glucagon-like peptide-1 receptor (GLP-1R) agonist and incretin mimetic used for the treatment of Type 2 diabetes mellitus. It has also been shown to have a beneficial role in the cardiovascular system. Here, we investigated the mechanism by which liraglutide promotes angiogenesis using human umbilical vein endothelial cells (HUVECs). HUVECs were treated with various concentrations of liraglutide, and assessed by wound healing assay and tube formation assay as measures of angiogenesis. We found that liraglutide at 10 and 100 nmol/L greatly promoted the angiogenic ability of HUVECs. Next, we examined the JAK2/STAT3 signaling pathway and found that liraglutide treatment led to JAK2/STAT3 activation and significant increase in the angiogenic mediator expressions, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and endothelial nitric oxide synthase (eNOS) in HUVECs. Treatment with JAK2 inhibitor, AG490, in HUVECs successfully reduced the observed effects of liraglutide. We conclude that liraglutide promotes the angiogenic ability of HUVECs by activating the JAK2/STAT3 signaling pathway and upregulating its downstream factors, VEGF, bFGF and eNOS. Thus, liraglutide may provide ischemic relief for diabetic patients with cardiovascular diseases in addition to glycemic control. •Liraglutide treatment promotes the angiogenic ability of HUVECs.•Liraglutide treatment activates the JAK2/STAT3 signaling pathway in HUVECs.•Liraglutide treatment enhances the expression of JAK2/STAT3 signaling pathway downstream genes, VEGF, bFGF and eNOS.