Two types of procoagulant platelets are formed upon physiological activation and are controlled by integrin α(IIb)β(3).
Autor: | Topalov NN; Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia., Yakimenko AO, Canault M, Artemenko EO, Zakharova NV, Abaeva AA, Loosveld M, Ataullakhanov FI, Nurden AT, Alessi MC, Panteleev MA |
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Jazyk: | angličtina |
Zdroj: | Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2012 Oct; Vol. 32 (10), pp. 2475-83. Date of Electronic Publication: 2012 Jul 26. |
DOI: | 10.1161/ATVBAHA.112.253765 |
Abstrakt: | Objective: Phosphatidylserine (PS) externalization by platelets upon activation is a key event in hemostasis and thrombosis. It is currently believed that strong stimulation of platelets forms 2 subpopulations, only 1 of which expresses PS. Methods and Results: Here, we demonstrate that physiological stimulation leads to the formation of not 1 but 2 types of PS-expressing activated platelets, with dramatically different properties. One subpopulation sustained increased calcium level after activation, whereas another returned to the basal low-calcium state. High-calcium PS-positive platelets had smaller size, high surface density of fibrin(ogen), no active integrin α(IIb)β(3), depolarized mitochondrial membranes, gradually lost cytoplasmic membrane integrity, and were poorly aggregated. In contrast, the low-calcium PS-positive platelets had normal size, retained mitochondrial membrane potential and cytoplasmic membrane integrity, and combined retention of fibrin(ogen) with active α(IIb)β(3) and high proaggregatory function. Formation of low-calcium PS-positive platelets was promoted by platelet concentration increase or shaking and was decreased by integrin α(IIb)β(3) antagonists, platelet dilution, or in platelets from kindlin-3-deficient and Glanzmann thrombasthenia patients. Conclusions: Identification of a novel PS-expressing platelet subpopulation with low calcium regulated by integrin α(IIb)β(3) can be important for understanding the mechanisms of PS exposure and thrombus formation. |
Databáze: | MEDLINE |
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