GLP-1 receptor expression in human internal thoracic arteries is dependent on low-grade inflammation potentially explaining the cardiovascular protective effect of GLP1-R agonists

Abstract Background Clinical research showed that glucagon-like peptide-1 receptor (GLP1R) agonists (GLP1RA) reduced the incidence of major cardiovascular events in diabetic patients. The protective effect was more noteworthy patients with established disease, associated chronic low-grade inflammation resulting endothelial dysfunction and arterial remodeling fibrosis. Despite clinically proven benefit GLP1RA, expression pattern GLP1R its function human vasculature remain poorly studied. Aim This study investigated role internal thoracic arteries (ITA) from coronary artery disease. Methods Human ITA were collected (N=30) undergoing bypass surgery at University Hospital Strasbourg. Gene levels assessed using RT-qPCR, protein by Western blot analysis, situ tissue localization proteins immunofluorescence (IF) staining, level oxidative stress dihydroethidium. Results a substantial difference mRNA reaching up to 7-fold among positively correlated those SLC5A1, SLC5A2, F3, AT1R, IL1B, IL6, TNFα, VCAM1 NCF1, negatively NOS3 levels. High expressing high phosphorylated p65 NF-κB, cell adhesion molecule VCAM1, members angiotensin system (ACE1 AT1R), fibrotic markers (MMP9, MMP2, TGFβ) low eNOS, whereas contrary observed for ITA. IF staining signals predominantly endothelium vascular smooth muscle Prominent CD68 perivascular adipose but not increased stress, which inhibited antioxidant N-acetylcysteine (NAC), NADPH oxidase inhibitor (VAS-2870), ACE (perindoprilat), AT1R antagonist (losartan), TNF-α neutralizing antibody (infliximab), selective SGLT2 (empagliflozin), dual SGLT1/2 (sotagliflozin) (liraglutide semaglutide) inhibitory effects amounting about 50 75%. Conclusion These findings indicate are dependent on linked dysfunction, pro-thrombotic, pro-remodeling pro-fibrotic responses. Furthermore, they sensitive inhibitors either local system, SGLT2, TNFα GLP1R. Thus, beneficial might be attributable their ability reduce pro-oxidant stimulatory signal related inflammation. Funding Acknowledgement Type funding sources: Other. Main source(s): Frency Society Vascular Medicine (SFMV)