OBJECTIVES: We investigated the role of P-selectin in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates. BACKGROUND: Plaque rupture followed by thrombus formation is a fundamental pathophysiology of acute coronary syndromes. Although the adhesive interaction between platelets and leukocytes via P-selectin is known to mediate platelet-rich thrombi, the true function of P-selectin in thrombus formation in vivo is unknown. METHODS: In wild-type (P(+/+)) and P-selectin-deficient (P(-/-)) mice with ferric chloride (FeCl(3))-induced carotid arterial thrombosis model, we measured in vivo platelet P-selectin expression and adenosine diphosphate (ADP)-induced ex vivo platelet aggregation. We also measured ex vivo ADP-induced whole blood aggregations and their size distribution by flow cytometry. RESULTS: Time to thrombotic occlusion was longer in P(-/-) mice than in P(+/+) mice. Spontaneous reflow after total thrombotic occlusion was observed in 8 of 10 P(-/-) mice but not in any P(+/+) mice. ADP-induced ex vivo platelet aggregation was not different between the two groups. However, ADP-induced ex vivo whole blood aggregation was inhibited in P(-/-) mice compared to P(+/+) mice. FeCl(3) application increased in vivo expressions of platelet P-selectin in P(+/+) mice but not in P(-/-) mice. The number of leukocytes within thrombi was less in P(-/-) mice than in P(+/+) mice. In flow cytometric analysis of size distribution of ADP-induced whole blood aggregates, the number of large aggregates was less in P(-/-) mice than in P(+/+) mice. Using platelet and leukocyte fluorescence makers, the large aggregates were confirmed as platelet-leukocyte aggregates. CONCLUSIONS: Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates.
OBJECTIVES: We investigated the role of P-selectin in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates. BACKGROUND: Plaque rupture followed by thrombus formation is a fundamental pathophysiology of acute coronary syndromes. Although the adhesive interaction between platelets and leukocytes via P-selectin is known to mediate platelet-rich thrombi, the true function of P-selectin in thrombus formation in vivo is unknown. METHODS: In wild-type (P(+/+)) and P-selectin-deficient (P(-/-)) mice with ferric chloride (FeCl(3))-induced carotid arterial thrombosis model, we measured in vivo platelet P-selectin expression and adenosine diphosphate (ADP)-induced ex vivo platelet aggregation. We also measured ex vivo ADP-induced whole blood aggregations and their size distribution by flow cytometry. RESULTS: Time to thrombotic occlusion was longer in P(-/-) mice than in P(+/+) mice. Spontaneous reflow after total thrombotic occlusion was observed in 8 of 10 P(-/-) mice but not in any P(+/+) mice. ADP-induced ex vivo platelet aggregation was not different between the two groups. However, ADP-induced ex vivo whole blood aggregation was inhibited in P(-/-) mice compared to P(+/+) mice. FeCl(3) application increased in vivo expressions of platelet P-selectin in P(+/+) mice but not in P(-/-) mice. The number of leukocytes within thrombi was less in P(-/-) mice than in P(+/+) mice. In flow cytometric analysis of size distribution of ADP-induced whole blood aggregates, the number of large aggregates was less in P(-/-) mice than in P(+/+) mice. Using platelet and leukocyte fluorescence makers, the large aggregates were confirmed as platelet-leukocyte aggregates. CONCLUSIONS: Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates.
Authors: Sarah C Starossom; Tatyana Veremeyko; Amanda W Y Yung; Marina Dukhinova; Cheryl Au; Alexander Y Lau; Howard L Weiner; Eugene D Ponomarev Journal: Circ Res Date: 2015-08-20 Impact factor: 17.367
Authors: Roman Covarrubias; Elena Chepurko; Adam Reynolds; Zachary M Huttinger; Ryan Huttinger; Katherine Stanfill; Debra G Wheeler; Tatiana Novitskaya; Simon C Robson; Karen M Dwyer; Peter J Cowan; Richard J Gumina Journal: Arterioscler Thromb Vasc Biol Date: 2016-07-14 Impact factor: 8.311
Authors: N Matijevic; K K Wu; A G Howard; B Wasserman; W Y-W Wang; A R Folsom; A R Sharrett Journal: Cerebrovasc Dis Date: 2011-04-12 Impact factor: 2.762
Authors: Michael Holinstat; Nancy E Colowick; Willie J Hudson; Dana Blakemore; Qingxia Chen; Heidi E Hamm; John H Cleator Journal: J Thromb Thrombolysis Date: 2013-02 Impact factor: 2.300
Authors: Riccardo Polosa; Mario Malerba; Rossella R Cacciola; Jaymin B Morjaria; Cinzia Maugeri; Gaetano Prosperini; Raimondo Gullo; Lucia Spicuzza; Alessandro Radaeli; Giuseppe U Di Maria Journal: Intern Emerg Med Date: 2011-06-10 Impact factor: 3.397
Authors: Jan Gert Nel; Chrisna Durandt; Timothy J Mitchell; Charles Feldman; Ronald Anderson; Gregory R Tintinger Journal: Lung Date: 2016-05-18 Impact factor: 2.584
Authors: Philip C Strike; Kesson Magid; Daisy L Whitehead; Lena Brydon; Mimi R Bhattacharyya; Andrew Steptoe Journal: Proc Natl Acad Sci U S A Date: 2006-03-02 Impact factor: 11.205