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PLoS One. 2015 Jun 8;10(6):e0129265. doi: 10.1371/journal.pone.0129265. eCollection 2015.

Platelet PI3Kγ Contributes to Carotid Intima-Media Thickening under Severely Reduced Flow Conditions.

Author information

1
Department of Cardiolog, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, 212001, P. R. China; Department of Neurosurgery, LSU Health Science Center, Shreveport, LA, 71103, United States of America.
2
Department of Neurosurgery, LSU Health Science Center, Shreveport, LA, 71103, United States of America.
3
Department of Cardiolog, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, 212001, P. R. China.

Abstract

Studies have begun to focus on the emerging function of platelets as immune and inflammatory cells that initiate and accelerate vascular inflammation. Phosphoinositide 3-kinase gamma (PI3Kγ) is critically involved in a number of inflammatory and autoimmune diseases. This study aims to investigate the contribution of platelet PI3Kγ to vascular remodeling under flow severely reduced conditions. Mouse partial left carotid artery ligation with adoptive transfer of activated, washed wild-type or PI3Kγ-/- platelets was used as the model. Intima-media area, leukocyte recruitment, and proinflammatory mediator expression were assessed. In vitro PI3Kγ-/- platelets were used to verify the effect of PI3Kγ on platelet activation, interaction with leukocytes, and endothelial cells. Mice injected with activated platelets showed a significant increase in intima-media thickening, recruitment of neutrophils (at 3 d) and macrophages (at 21 d), and intercellular adhesion molecule-1, vascular cell adhesion molecule-1, tumor necrosis factor alpha, and interleukin-6 expression (at 3 d) in the flow-reduced area. These effects were abrogated by platelet PI3Kγ deficiency. Circulating platelet-leukocyte aggregates were reduced in PI3Kγ-/- mice after partial ligation. In vivo data confirmed that PI3Kγ mediated Adenine di-Phosphate -induced platelet activation through the Akt and p38 MAP kinase signaling pathways. Moreover, platelet PI3Kγ deficiency reduced platelet-leukocyte aggregation and platelet-endothelial cell (EC) interaction. These findings indicate that platelet PI3Kγ contributes to platelet-mediated vascular inflammation and carotid intima-media thickening after flow severely reduced. Platelet PI3Kγ may be a new target in the treatment of vascular diseases.

PMID:
26053836
PMCID:
PMC4459692
DOI:
10.1371/journal.pone.0129265
[Indexed for MEDLINE]
Free PMC Article

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