Impacts of Semaglutide on Monocyte–Endothelial Crosstalk in Atherosclerosis Pathophysiology

Atherosclerosis is a chronic inflammatory disease and the leading cause of cardiovascular morbidity and mortality. A critical early step in its development is the adhesion of circulating monocytes to activated vascular endothelial cells, followed by their migration into the vessel wall, where they contribute to plaque formation.

Semaglutide, a GLP-1 receptor agonist widely used for type 2 diabetes and obesity, has been shown in large clinical trials (SUSTAIN-6 and SELECT) to significantly reduce major adverse cardiovascular events. Importantly, these benefits extend beyond glycemic control, suggesting additional direct vascular protective mechanisms; however, the underlying cellular basis remains unclear.

This study investigates whether semaglutide directly modulates monocyte–endothelial interactions under inflammatory conditions. Using an in-vitro model of EA.hy926 endothelial cells and THP-1 monocytes, vascular inflammation will be induced with TNF-α to mimic early atherosclerotic activation. We will assess whether semaglutide reduces monocyte adhesion to endothelial cells and limits monocyte migration across an endothelial barrier. Effects will be compared against PBS (negative control) and atorvastatin (positive control).

This work aims to define how semaglutide influences immune–vascular interactions and provide mechanistic insight into its cardiovascular protective effects.