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- Title
Glucagon-Like Peptide 1 Receptor Activation Attenuates Platelet Aggregation and Thrombosis.
- Authors
Cameron-Vendrig, Alison; Reheman, Adili; Ahsan Siraj, M.; Xiaohong Ruby Xu; Yiming Wang; Xi Lei; Afroze, Talat; Shikatani, Eric; El-Mounayri, Omar; Noyan, Hossein; Weissleder, Ralph; Heyu Ni; Husain, Mansoor; Siraj, M Ahsan; Xu, Xiaohong Ruby; Wang, Yiming; Lei, Xi; Ni, Heyu
- Abstract
Short-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.
- Subjects
GLUCAGON-like peptide-1 receptor; THROMBOSIS; MEGAKARYOCYTES; CELL lines; EXENATIDE; NITRIC-oxide synthases; THROMBOSIS prevention; ANIMAL experimentation; BLOOD platelet aggregation; LUNGS; MICE; OXIDOREDUCTASES; PANCREAS; PEPTIDES; RESEARCH funding; VENOM; GLUCAGON-like peptide 1; PLATELET aggregation inhibitors; PHARMACODYNAMICS
- Publication
Diabetes, 2016, Vol 65, Issue 6, p1714
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db15-1141