Glucagon-Like Peptide 1 Receptor Activation Attenuates Platelet Aggregation and Thrombosis
Siraj, M. Ahsan
Xu, Xiaohong Ruby
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CitationCameron-Vendrig, Alison, Adili Reheman, M. Ahsan Siraj, Xiaohong Ruby Xu, Yiming Wang, Xi Lei, Talat Afroze, et al. 2016. “Glucagon-Like Peptide 1 Receptor Activation Attenuates Platelet Aggregation and Thrombosis.” Diabetes 65 (6): 1714–23. https://doi.org/10.2337/db15-1141.
AbstractShort-term studies in subjects with diabetes receiving glucagon-like peptide 1 (GLP-1)-targeted therapies have suggested a reduced number of cardiovascular events. The mechanisms underlying this unexpectedly rapid effect are not known. We cloned full-length GLP-1 receptor (GLP-1R) mRNA from a human megakaryocyte cell line (MEG-01), and found expression levels of GLP-1Rs in MEG-01 cells to be higher than those in the human lung but lower than in the human pancreas. Incubation with GLP-1 and the GLP-1R agonist exenatide elicited a cAMP response in MEG-01 cells, and exenatide significantly inhibited thrombin-, ADP-, and collagen-induced platelet aggregation. Incubation with exenatide also inhibited thrombus formation under flow conditions in ex vivo perfusion chambers using human and mouse whole blood. In a mouse cremaster artery laser injury model, a single intravenous injection of exenatide inhibited thrombus formation in normoglycemic and hyperglycemic mice in vivo. Thrombus formation was greater in mice transplanted with bone marrow lacking a functional GLP-1R (Glp1r(-/-)) compared with those receiving wild-type bone marrow. Although antithrombotic effects of exenatide were partly lost in mice transplanted with bone marrow from Glp1r(-/-) mice, they were undetectable in mice with a genetic deficiency of endothelial nitric oxide synthase. The inhibition of platelet function and the prevention of thrombus formation by GLP-1R agonists represent potential mechanisms for reduced atherothrombotic events.
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