1. Academic Validation
  2. 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

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

  • Mol Immunol. 2019 Dec;116:73-79. doi: 10.1016/j.molimm.2019.09.021.
Wei Chang 1 Fu Zhu 2 Hongchao Zheng 2 Zhiwen Zhou 2 Peizhi Miao 2 Lifang Zhao 2 Zhenzhen Mao 2
Affiliations

Affiliations

  • 1 Department of Cardiology, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China; Shanghai Clinical Research Center, Chinese Academy of Sciences, Shanghai, 200031, China. Electronic address: wchang6021@163.com.
  • 2 Department of Cardiology, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China; Shanghai Clinical Research Center, Chinese Academy of Sciences, Shanghai, 200031, China.
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.

Keywords

Atherosclerosis; Krüppel-like factor 2; Oxidized low-density lipoprotein; Vascular cellular adhesion molecule 1 (VCAM-1).

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