Compression force sensing regulates integrin αIIbβ3 adhesive function on diabetic platelets
| العنوان: | Compression force sensing regulates integrin αIIbβ3 adhesive function on diabetic platelets |
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| المؤلفون: | Brianna Coulter, Yunfeng Chen, Saheb Al-Daher, Lining Ju, Eric I. Felner, Shaun P. Jackson, Mark E. Cooper, Lotte Lindhardt Tonnesen, Yuping Yuan, Neale Cohen, Cheng Zhu, James D. McFadyen, Sophie Maiocchi, Anna C. Calkin, Simone M. Schoenwaelder, Imala Alwis |
| المصدر: | Nature Communications, Vol 9, Iss 1, Pp 1-16 (2018) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Blood Platelets, Male, Ticlopidine, Platelet Aggregation, Science, Integrin, General Physics and Astronomy, chemistry.chemical_element, Platelet Glycoprotein GPIIb-IIIa Complex, Calcium, Fibrinogen, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Mice, Phosphatidylinositol 3-Kinases, Platelet Adhesiveness, Diabetes mellitus, medicine, Animals, Humans, Platelet, Platelet activation, lcsh:Science, Multidisciplinary, biology, Aspirin, Chemistry, Biological membrane, Thrombosis, General Chemistry, Middle Aged, medicine.disease, Clopidogrel, 3. Good health, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, Diabetes Mellitus, Type 1, biology.protein, lcsh:Q, Female, medicine.drug |
| الوصف: | Diabetes is associated with an exaggerated platelet thrombotic response at sites of vascular injury. Biomechanical forces regulate platelet activation, although the impact of diabetes on this process remains ill-defined. Using a biomembrane force probe (BFP), we demonstrate that compressive force activates integrin αIIbβ3 on discoid diabetic platelets, increasing its association rate with immobilized fibrinogen. This compressive force-induced integrin activation is calcium and PI 3-kinase dependent, resulting in enhanced integrin affinity maturation and exaggerated shear-dependent platelet adhesion. Analysis of discoid platelet aggregation in the mesenteric circulation of mice confirmed that diabetes leads to a marked enhancement in the formation and stability of discoid platelet aggregates, via a mechanism that is not inhibited by therapeutic doses of aspirin and clopidogrel, but is eliminated by PI 3-kinase inhibition. These studies demonstrate the existence of a compression force sensing mechanism linked to αIIbβ3 adhesive function that leads to a distinct prothrombotic phenotype in diabetes. Diabetes is associated with an increased thrombotic response, but the mechanism is unknown. Here the authors demonstrate that compressive force activates integrin αIIbβ3 on discoid diabetic platelets and that platelet aggregates can be eliminated by PI 3-kinase inhibition, but not by anti-thrombotics aspirin or clopidogrel. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ff83fa89242db782aa93004f627ca154 https://doaj.org/article/39fb3cca5ca9489ba78bd4ef5db73aba |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ff83fa89242db782aa93004f627ca154 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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