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Glycoprotein Ib clustering in platelets can be inhibited by alpha-linolenic acid as revealed by cryo-electron tomography


Stivala, Simona; Sorrentino, Simona; Gobbato, Sara; Bonetti, Nicole R; Camici, Giovanni G; Lüscher, Thomas F; Medalia, Ohad; Beer, Jürg H (2020). Glycoprotein Ib clustering in platelets can be inhibited by alpha-linolenic acid as revealed by cryo-electron tomography. Haematologica, 105(6):1660-1666.

Abstract

Platelet adhesion to the sub-endothelial matrix and damaged endothelium occurs through a multi-step process mediated in the initial phase by glycoprotein Ib binding to von Willebrand factor, which leads to the subsequent formation of a platelet plug. The plant-derived omega-3 fatty acid alpha-linolenic acid is an abundant alternative to fish-derived n-3 FA and has anti-inflammatory and anti-thrombotic properties. In this study, we investigated the impact of alpha-linolenic acid on human platelet binding to vWF under high-shear flow conditions (mimicking blood flow in stenosed arteries). Pre-incubation of fresh human blood from healthy donors with alpha-linolenic acid at dietary relevant concentrations reduced platelet binding and rolling on vWF-coated microchannels at a shear rate of 100 dyn/cm2. Depletion of membrane cholesterol by incubation of platelet-rich-plasma with methyl-beta cyclodextrin abrogated platelet rolling on vWF. Analysis of glycoprotein Ib by applying cryo-electron tomography to intact platelets revealed local clusters of glycoprotein Ib complexes, upon shear-force exposure, whose formation could be prevented by alpha-linolenic acid treatment. This study provides novel findings on the rapid local rearrangement of the glycoprotein Ib complexes in response to high-shear flow and highlights the mechanism of in vitro inhibition of platelet binding to and rolling on vWF by alpha-linolenic acid.

Abstract

Platelet adhesion to the sub-endothelial matrix and damaged endothelium occurs through a multi-step process mediated in the initial phase by glycoprotein Ib binding to von Willebrand factor, which leads to the subsequent formation of a platelet plug. The plant-derived omega-3 fatty acid alpha-linolenic acid is an abundant alternative to fish-derived n-3 FA and has anti-inflammatory and anti-thrombotic properties. In this study, we investigated the impact of alpha-linolenic acid on human platelet binding to vWF under high-shear flow conditions (mimicking blood flow in stenosed arteries). Pre-incubation of fresh human blood from healthy donors with alpha-linolenic acid at dietary relevant concentrations reduced platelet binding and rolling on vWF-coated microchannels at a shear rate of 100 dyn/cm2. Depletion of membrane cholesterol by incubation of platelet-rich-plasma with methyl-beta cyclodextrin abrogated platelet rolling on vWF. Analysis of glycoprotein Ib by applying cryo-electron tomography to intact platelets revealed local clusters of glycoprotein Ib complexes, upon shear-force exposure, whose formation could be prevented by alpha-linolenic acid treatment. This study provides novel findings on the rapid local rearrangement of the glycoprotein Ib complexes in response to high-shear flow and highlights the mechanism of in vitro inhibition of platelet binding to and rolling on vWF by alpha-linolenic acid.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
04 Faculty of Medicine > Center for Molecular Cardiology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 June 2020
Deposited On:21 Jan 2020 13:57
Last Modified:29 Jul 2020 12:54
Publisher:Ferrata Storti Foundation
ISSN:0390-6078
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3324/haematol.2019.220988
PubMed ID:31439672

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