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GLP-1 receptor agonists and atherosclerosis protection: the vascular endothelium takes center stage.

Authors :
Park, Brady
Bakbak, Ehab
Teoh, Hwee
Krishnaraj, Aishwarya
Dennis, Fallon
Quan, Adrian
Rotstein, Ori D.
Butler, Javed
Hess, David A.
Verma, Subodh
Source :
American Journal of Physiology: Heart & Circulatory Physiology; May2024, Vol. 326 Issue 5, pH1159-H1176, 18p
Publication Year :
2024

Abstract

Atherosclerotic cardiovascular disease is a chronic condition that often copresents with type 2 diabetes and obesity. Glucagonlike peptide-1 receptor agonists (GLP-1RAs) are incretin mimetics endorsed by major professional societies for improving glycemic status and reducing atherosclerotic risk in people living with type 2 diabetes. Although the cardioprotective efficacy of GLP-1RAs and their relationship with traditional risk factors are well established, there is a paucity of publications that have summarized the potentially direct mechanisms through which GLP-1RAs mitigate atherosclerosis. This review aims to narrow this gap by providing comprehensive and in-depth mechanistic insight into the antiatherosclerotic properties of GLP-1RAs demonstrated across large outcome trials. Herein, we describe the landmark cardiovascular outcome trials that triggered widespread excitement around GLP-1RAs as a modern class of cardioprotective agents, followed by a summary of the origins of GLP-1RAs and their mechanisms of action. The effects of GLP-1RAs at each major pathophysiological milestone of atherosclerosis, as observed across clinical trials, animal models, and cell culture studies, are described in detail. Specifically, this review provides recent preclinical and clinical evidence that suggest GLP-1RAs preserve vessel health in part by preventing endothelial dysfunction, achieved primarily through the promotion of angiogenesis and inhibition of oxidative stress. These protective effects are in addition to the broad range of atherosclerotic processes GLP-1RAs target downstream of endothelial dysfunction, which include systemic inflammation, monocyte recruitment, proinflammatory macrophage and foam cell formation, vascular smooth muscle cell proliferation, and plaque development. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03636135
Volume :
326
Issue :
5
Database :
Complementary Index
Journal :
American Journal of Physiology: Heart & Circulatory Physiology
Publication Type :
Academic Journal
Accession number :
177142290
Full Text :
https://doi.org/10.1152/ajpheart.00574.2023