Expression of GLP1 Receptor on Peripheral Blood Mononuclear Cells in Advanced Peripheral Artery Disease: Paving the Way for GLP1R Agonists Treatment in Chronic Limb Threatening Ischemia

Overview

The goal of this observational study is to learn whether activation of the GLP-1 receptor could represent a therapeutic target by characterizing its expression and associated inflammatory mechanisms in patients with peripheral artery disease, according to disease severity, in adults with symptomatic lower-limb peripheral arterial disease. The main questions it aims to answer are: * Is the level of GLP-1 receptor (GLP1R) expression on peripheral blood mononuclear cells (PBMC) different between patients with intermittent claudication (ischemia of effort) and those with chronic limb-threatening ischemia? * Is GLP1R expression associated with inflammatory and oxidative profiles of PBMC? * Can GLP-1 receptor agonists reverse inflammatory and oxidative alterations induced by plasma from patients with peripheral artery disease in endothelial cell cultures? * Are there specific plasma proteomic signatures associated with GLP1R overexpression? Researchers will compare patients with intermittent claudication to patients with chronic limb-threatening ischemia to see if disease severity is associated with differences in GLP1R expression, PBMC inflammatory/oxidative phenotype, and plasma proteomic profiles. Participants will: * Provide an additional blood sample (15 mL) collected during a routine, clinically indicated blood draw * Have PBMC isolated for measurement of GLP1R expression and assessment of inflammatory and oxidative markers * Have plasma analyzed for proteomic profiling and used in in-vitro endothelial cell experiments Participation ends after completion of the blood sampling, and no additional procedures beyond standard clinical care are required.

Chronic limb-threatening ischemia is the most severe stage of lower-limb peripheral arterial disease and remains associated with poor cardiovascular and limb prognosis. This condition is characterized by a pronounced systemic inflammatory and oxidative state, in which peripheral blood mononuclear cells play a central role. Glucagon-like peptide-1 receptor agonists have shown anti-inflammatory and cardiovascular protective effects in other settings, but the involvement of the GLP-1 receptor in severe peripheral arterial disease has not been clearly established. This pilot study aims to characterize GLP-1 receptor expression on peripheral blood mononuclear cells according to disease severity and to evaluate its association with inflammatory, oxidative, and proteomic profiles. This is a monocentric, cross-sectional observational study conducted at the CHU of Strasbourg. Patients hospitalized for evaluation of symptomatic lower-limb peripheral arterial disease will be classified into intermittent claudication or chronic limb-threatening ischemia groups. A single additional blood sample will be collected during routine clinical sampling. Peripheral blood mononuclear cells and plasma will be analyzed to assess GLP-1 receptor expression, inflammatory and oxidative markers, and plasma proteomic signatures. Exploratory in-vitro experiments will evaluate the ability of GLP-1 receptor agonists to reverse endothelial alterations induced by patient plasma. The study is designed to generate mechanistic data supporting the GLP-1 receptor as a potential therapeutic target in chronic limb-threatening ischemia and to inform future interventional studies.