Platelet and Myeloid Cell Phenotypes in a Rat Model of Fabry Disease

Overview

Journal FASEB J

Specialties Biology
Physiology

Date 2021 Jul 28

PMID 34320241

Citations 2

Authors

Adam J Kanack

Kazuhiro Aoki

Michael Tiemeyer

Nancy M Dahms

Affiliations

Soon will be listed here.

Abstract

Fabry disease results from a deficiency of the lysosomal enzyme ⍺-Galactosidase-A (⍺-Gal A) and is estimated to occur in approximately 1:4100 live births. Characteristic of the disease is the accumulation of α-Gal-A substrates, primarily the glycosphingolipids (GSLs) globotriaosylceramide and globotriaosylsphingosine. Thrombotic events are a significant concern for Fabry patients, with strokes contributing to a significant decrease in overall lifespan. Currently, the mechanisms underlying the increased risk of thrombotic events experienced by Fabry patients are incompletely defined. Using a rat model of Fabry disease, we provide an improved understanding of the mechanisms linking GSL accumulation to thrombotic risk. We found that ⍺-Gal A-deficient rats accumulate myeloid-derived leukocytes at sites of GSL accumulation, including in the bone marrow and circulation, and that myeloid-derived leukocyte and megakaryocyte populations were prominent among cell types that accumulated GSLs. In the circulation, ⍺-Gal A-deficient rats had increases in cytokine-producing cell types and a corresponding elevation of pro-inflammatory cytokines. Lastly, circulating platelets from ⍺-Gal A-deficient rats accumulated a similar set of ⍺-Galactosidase-A substrates as was observed in megakaryocytes in the bone marrow, and exhibited increased platelet binding to fibrinogen in microfluidic and flow cytometric assays.

Citing Articles

Glycosphingolipids and their impact on platelet activity in a murine model of fabry disease.

Kanack A, Prodoehl E, Ishihara-Aoki M, Aoki K, Dahms N Sci Rep. 2024; 14(1):29488.

PMID: 39604471 PMC: 11603304. DOI: 10.1038/s41598-024-80633-6.

Platelets in Alcohol-Associated Liver Disease: Interaction With Neutrophils.

Wang J, Wang X, Peng H, Dong Z, Liangpunsakul S, Zuo L Cell Mol Gastroenterol Hepatol. 2024; 18(1):41-52.

PMID: 38461963 PMC: 11127035. DOI: 10.1016/j.jcmgh.2024.03.001.

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