Liraglutide Lowers Endothelial Vascular Cell Adhesion Molecule-1 in Murine Atherosclerosis Independent of Glucose Levels

Mukesh Punjabi; Alexandra Kosareva; Lifen Xu; Amanda Ochoa-Espinosa; Sarah Decembrini; Georg Hofmann; Samira Wyttenbach; Bidda Rolin; Michael Nyberg; Beat A Kaufmann

doi:10.1016/j.jacbts.2022.08.002

Liraglutide Lowers Endothelial Vascular Cell Adhesion Molecule-1 in Murine Atherosclerosis Independent of Glucose Levels

JACC Basic Transl Sci. 2022 Dec 7;8(2):189-200. doi: 10.1016/j.jacbts.2022.08.002. eCollection 2023 Feb.

Authors

Affiliations

¹ Cardiovascular Molecular Imaging, Department of Biomedicine, University of Basel, Basel, Switzerland.
² Global Drug Discovery, Novo Nordisk A/S, Maaloev, Denmark.
³ Department of Cardiology, University Hospital and University of Basel, Basel, Switzerland.

Abstract

The authors determined the effect of the GLP-1 receptor agonist liraglutide on endothelial surface expression of vascular cell adhesion molecule (VCAM)-1 in murine apolipoprotein E knockout atherosclerosis. Contrast-enhanced ultrasound molecular imaging using microbubbles targeted to VCAM-1 and control microbubbles showed a 3-fold increase in endothelial surface VCAM-1 signal in vehicle-treated animals, whereas in the liraglutide-treated animals the signal ratio remained around 1 throughout the study. Liraglutide had no influence on low-density lipoprotein cholesterol or glycated hemoglobin, but reduced TNF-α, IL-1β, MCP-1, and OPN. Aortic plaque lesion area and luminal VCAM-1 expression on immunohistology were reduced under liraglutide treatment.

Keywords: ApoE, apolipoprotein E; CEUMI, contrast-enhanced ultrasound molecular imaging; CVD, cardiovascular disease; GLP, glucagon-like peptide; GLP-1R, glucagon-like peptide-1 receptor; GLP-1RA, glucagon-like peptide-1 receptor agonist; HDL-C, high-density lipoprotein cholesterol; HbA1c, glycated hemoglobin; ICAM, intercellular cell adhesion molecule; IL, interleukin; LDL-C, low-density lipoprotein cholesterol; MB, microbubble; MBCtr, control microbubbles; MBVCAM-1, microbubbles targeted to VCAM; MCP, monocyte chemoattractant protein; OPN, osteopontin; TG, triglycerides; TGRL, triglyceride-rich lipoproteins; TNF, tumor necrosis factor; VCAM, vascular cell adhesion molecule; VLDL-C, very low-density lipoprotein cholesterol; atherosclerosis; liraglutide; molecular imaging; ultrasound.