التفاصيل البيبلوغرافية
| العنوان: |
Glucagon-Like Peptide 1 Receptor Activation Attenuates Platelet Aggregation and Thrombosis. |
| المؤلفون: |
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 |
| المصدر: |
Diabetes; Jun2016, Vol. 65 Issue 6, p1714-1723, 10p |
| مصطلحات موضوعية: |
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 |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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