التفاصيل البيبلوغرافية
| العنوان: |
Compression force sensing regulates integrin αIIbβ3 adhesive function on diabetic platelets. |
| المؤلفون: |
Lining Ju, McFadyen, James D., Al-Daher, Saheb, Alwis, Imala, Yunfeng Chen, Tønnesen, Lotte L., Maiocchi, Sophie, Coulter, Brianna, Calkin, Anna C., Felner, Eric I., Neale Cohen, Yuping Yuan, Schoenwaelder, Simone M., Cooper, Mark E., Cheng Zhu, Jackson, Shaun P. |
| المصدر: |
Nature Communications; 3/14/2018, Vol. 9 Issue 1, p1-16, 16p, 1 Chart, 7 Graphs |
| مستخلص: |
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 ααIIbβ3 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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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