The role of PI3K/Akt signaling pathway in non-physiological shear stress-induced platelet activation.
Artif Organs
; 43(9): 897-908, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-30972780
ABSTRACT
The PI3K/Akt signaling pathway has been implicated in playing an important role in platelet activation during hemostasis and thrombosis involving platelet-matrix interaction and platelet aggregation. Its role in non-physiological shear stress (NPSS)-induced platelet activation relevant to high-shear blood contacting medical devices (BCMDs) is unclear. In the context of blood cells flowing in BCMDs, platelets are subjected to NPSS (>100 Pa) with very short exposure time (<1 s). In this study, we investigated whether NPSS with short exposure time induces platelet activation through the PI3K/Akt signaling pathway. Healthy donor blood treated with or without PI3K inhibitor was subjected to NPSS (150 Pa) with short exposure time (0.5 s). Platelet activation indicated by the surface P-selectin expression and activated glycoprotein (GP) IIb/IIIa was quantified using flow cytometry. The phosphorylation of Akt, activation of the PI3K signaling, was characterized by western blotting. Changes in adhesion behavior of NPSS-sheared platelets on fibrinogen, collagen, and von Willebrand factor (vWF) were quantified with fluorescent microscopy by perfusing the NPSS-sheared and PI3K inhibitor-treated blood through fibrinogen, collagen, and vWF-coated microcapillary tubes. The results showed that the PI3K/Akt signaling was involved with both NPSS-induced platelet activation and platelet-matrix interaction. NPSS-sheared platelets exhibited exacerbated platelet adhesion on fibrinogen, but had diminished platelet adhesion on collagen and vWF. The inhibition of PI3K signaling reduced P-selectin expression and GPIIb/IIIa activation with suppressed Akt phosphorylation and abolished NPSS-enhanced platelet adhesion on fibrinogen in NPSS-sheared blood. The inhibition of PI3K signaling can attenuate the adhesion of unsheared platelets (baseline) on collagen and vWF, while had no impact on adhesion of NPSS-sheared platelets on collagen and vWF. This study confirmed the important role of PI3K/Akt signaling pathway in NPSS-induced platelet activation. The finding of this study suggests that blocking PI3K/Akt signaling pathway could be a potential method to treat thrombosis in patients implanted with BCMDs.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
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Transdução de Sinais
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Ativação Plaquetária
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Fosfatidilinositol 3-Quinases
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Proteínas Proto-Oncogênicas c-akt
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article