Semaglutide | Semaglutide modulates prothrombotic and atherosclerotic mechanisms, associated with epicardial fat, neutrophils and endothelial cells network | springermedicine.com

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Cardiovascular Diabetology

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Open Access 01-12-2024 | Semaglutide | Research

Semaglutide modulates prothrombotic and atherosclerotic mechanisms, associated with epicardial fat, neutrophils and endothelial cells network

Authors: David García-Vega, David Sánchez-López, Gemma Rodríguez-Carnero, Rocío Villar-Taibo, Juan E. Viñuela, Adán Lestegás-Soto, Ana Seoane-Blanco, María Moure-González, Susana B. Bravo, Ángel L. Fernández, José R. González-Juanatey, Sonia Eiras

Published in: Cardiovascular Diabetology | Issue 1/2024

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Abstract

Background

Obesity has increased in recent years with consequences on diabetes and other comorbidities. Thus, 1 out of 3 diabetic patients suffers cardiovascular disease (CVD). The network among glucose, immune system, endothelium and epicardial fat has an important role on pro-inflammatory and thrombotic mechanisms of atherogenesis. Since semaglutide, long-acting glucagon like peptide 1- receptor agonist (GLP-1-RA), a glucose-lowering drug, reduces body weight, we aimed to study its effects on human epicardial fat (EAT), aortic endothelial cells and neutrophils as atherogenesis involved-cardiovascular cells.

Methods

EAT and subcutaneous fat (SAT) were collected from patients undergoing cardiac surgery. Differential glucose consumption and protein cargo of fat-released exosomes, after semaglutide or/and insulin treatment were analyzed by enzymatic and TripleTOF, respectively. Human neutrophils phenotype and their adhesion to aortic endothelial cells (HAEC) or angiogenesis were analyzed by flow cytometry and functional fluorescence analysis. Immune cells and plasma protein markers were determined by flow cytometry and Luminex-multiplex on patients before and after 6 months treatment with semaglutide.

Results

GLP-1 receptor was expressed on fat and neutrophils. Differential exosomes-protein cargo was identified on EAT explants after semaglutide treatment. This drug increased secretion of gelsolin, antithrombotic protein, by EAT, modulated CD11b on neutrophils, its migration and endothelial adhesion, induced by adiposity protein, FABP4, or a chemoattractant. Monocytes and neutrophils phenotype and plasma adiposity, stretch, mesothelial, fibrotic, and inflammatory markers on patients underwent semaglutide treatment for 6 months showed a 20% reduction with statistical significance on FABP4 levels and an 80% increase of neutrophils-CD88.

Conclusion

Semaglutide increases endocrine activity of epicardial fat with antithrombotic properties. Moreover, this drug modulates the pro-inflammatory and atherogenic profile induced by the adiposity marker, FABP4, which is also reduced in patients after semaglutide treatment.

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Title: Semaglutide modulates prothrombotic and atherosclerotic mechanisms, associated with epicardial fat, neutrophils and endothelial cells network
Authors: David García-Vega
David Sánchez-López
Gemma Rodríguez-Carnero
Rocío Villar-Taibo
Juan E. Viñuela
Adán Lestegás-Soto
Ana Seoane-Blanco
María Moure-González
Susana B. Bravo
Ángel L. Fernández
José R. González-Juanatey
Sonia Eiras
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Semaglutide
Insulins
Insulins
Obesity
Obesity
Arterial Occlusive Disease
Published in: Cardiovascular Diabetology / Issue 1/2024
Electronic ISSN: 1475-2840
DOI: https://doi.org/10.1186/s12933-023-02096-9

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