Platelet PI3K? Contributes to Carotid Intima-Media Thickening under Severely Reduced Flow Conditions.

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 (PI3K?) is critically involved in a number of inflammatory and autoimmune diseases. This study aims to investigate the contribution of platelet PI3K? to vascular remodeling under flow severely reduced conditions. Mouse partial left carotid artery ligation with adoptive transfer of activated, washed wild-type or PI3K?-/- platelets was used as the model. Intima-media area, leukocyte recruitment, and proinflammatory mediator expression were assessed. In vitro PI3K?-/- platelets were used to verify the effect of PI3K? 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 PI3K? deficiency. Circulating platelet-leukocyte aggregates were reduced in PI3K?-/- mice after partial ligation. In vivo data confirmed that PI3K? mediated Adenine di-Phosphate -induced platelet activation through the Akt and p38 MAP kinase signaling pathways. Moreover, platelet PI3K? deficiency reduced platelet-leukocyte aggregation and platelet-endothelial cell (EC) interaction. These findings indicate that platelet PI3K? contributes to platelet-mediated vascular inflammation and carotid intima-media thickening after flow severely reduced. Platelet PI3K? may be a new target in the treatment of vascular diseases.

SUBMITTER: Wang C 

PROVIDER: S-EPMC4459692 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature