Glucagon-like peptide-1 receptor agonist dulaglutide prevents ox-LDL-induced adhesion of monocytes to human endothelial cells: An implication in the treatment of atherosclerosis. (December 2019)

• Record Type: Journal Article
• Authors: Chang, Wei; Zhu, Fu; Zheng, Hongchao; Zhou, Zhiwen; Miao, Peizhi; Zhao, Lifang; Mao, Zhenzhen
• Is Part Of: Molecular immunology. Volume 116(2019:Dec.)
• Page Start: 73
• Page End: 79
• Publication Date: 2019-12
• Subjects: Atherosclerosis -- Oxidized low-density lipoprotein -- Vascular cellular adhesion molecule 1 (VCAM-1) -- Krüppel-like factor 2; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2019.09.021
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: Dulaglutide ameliorated ox-LDL-induced oxidative stress and mitochondrial dysfunction. Dulaglutide suppressed ox-LDL-induced secretion of IL-1β, IL-6, MCP-1, and HMG-1. Dulaglutide suppressed ox-LDL-induced reduction of cell viability and release of LDH. Dulaglutide suppressed attachment of THP-1 to HAECs by inhibiting VCAM-1, E-selectin. Dulaglutide promoted the expression of KLF2 through inhibiting the activation of p53. Abstract: Atherosclerosis is a common comorbidity of type II diabetes and a leading cause of death worldwide. The presence of oxidized low-density lipoprotein (ox-LDL) drives atherogenesis by inducing oxidative stress, mitochondrial dysfunction, expression of proinflammatory cytokines and chemokines including interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein 1 (MCP-1), adhesion molecules including vascular cellular adhesion molecule 1 (VCAM-1) and E-selectin, and downregulating expression of the Krüppel-like factor 2 (KLF2) transcription factor. Importantly, ox-LDL induced the attachment of THP-1 monocytes to endothelial cells. In the present study, we demonstrate for the first time that the specific glucagon-like peptide 1 receptor (GLP-1R) agonist dulaglutide may prevent these atherosclerotic effects of ox-LDL by preventing suppression of KLF2 by p53 protein in human aortic endothelial cells. KLF2 has been shown to play a major role in protecting vascular endothelial cells from damage induced by ox-LDL and oscillatory shear, and therefore, therapies capable of mediating KLF2 signaling may be an attractive treatment option for preventing the development and progression of atherosclerosis.