Glycoprotein Ib clustering in platelets can be inhibited by α-linolenic acid as revealed by cryo-electron tomography
| Autor: | Jürg H. Beer, Nicole R. Bonetti, Simona Stivala, Thomas F. Lüscher, Sara Gobbato, Ohad Medalia, Giovanni G. Camici, Simona Sorrentino |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Blood Platelets
Electron Microscope Tomography Endothelium Matrix (biology) Platelet Biology & its Disorders 03 medical and health sciences 0302 clinical medicine Von Willebrand factor Antithrombotic von Willebrand Factor medicine Animals Cluster Analysis Humans Platelet chemistry.chemical_classification biology Chemistry Fatty acid alpha-Linolenic Acid Hematology Articles In vitro medicine.anatomical_structure Glycoprotein Ib Platelet Glycoprotein GPIb-IX Complex biology.protein Biophysics 030215 immunology |
| Zdroj: | Haematologica |
| ISSN: | 1592-8721 0390-6078 |
| Popis: | 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 (vWF), which leads to the subsequent formation of a platelet plug. The plant-derived ω-3 fatty acid α-linolenic acid is an abundant alternative to fish-derived n-3 fatty acids and has anti-inflammatory and antithrombotic properties. In this study, we investigated the impact of α-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 α-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-β 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 exposure to shear force: the formation of these complexes could be prevented by treatment with α-linolenic acid. This study provides novel findings on the rapid local rearrangement of 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 α-linolenic acid. |
| Databáze: | OpenAIRE |
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