Superoxide Dismutase 2 is dispensable for platelet function

Trevor P. Fidler; Jesse W. Rowley; Claudia Araujo; Luc H. Boudreau; Alex Marti; Rhonda Souvenir; Kali Dale; Eric Boilard; Andrew S. Weyrich; E. Dale Abel

doi:10.1160/TH17-03-0174

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2017; 117(10): 1859-1867
DOI: 10.1160/TH17-03-0174

Cellular Haemostasis and Platelets

Schattauer GmbH

Superoxide Dismutase 2 is dispensable for platelet function

Trevor P. Fidler

¹Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA

²Program in Molecular Medicine University of Utah, Salt Lake City, Utah, USA

³Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

,

Jesse W. Rowley

²Program in Molecular Medicine University of Utah, Salt Lake City, Utah, USA

,

Claudia Araujo

²Program in Molecular Medicine University of Utah, Salt Lake City, Utah, USA

,

Luc H. Boudreau

⁴Department of Infectious Diseases and Immunity, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l’Université Laval, Quebec City, Quebec, Canada

,

Alex Marti

³Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

,

Rhonda Souvenir

³Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

,

Kali Dale

²Program in Molecular Medicine University of Utah, Salt Lake City, Utah, USA

,

Eric Boilard

⁴Department of Infectious Diseases and Immunity, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l’Université Laval, Quebec City, Quebec, Canada

,

Andrew S. Weyrich

²Program in Molecular Medicine University of Utah, Salt Lake City, Utah, USA

,

E. Dale Abel

²Program in Molecular Medicine University of Utah, Salt Lake City, Utah, USA

³Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

› Author Affiliations

Abstract

Summary

Increased intracellular reactive oxygen species (ROS) promote platelet activation. The sources of platelet-derived ROS are diverse and whether or not mitochondrial derived ROS, modulates platelet function is incompletely understood. Studies of platelets from patients with sickle cell disease, and diabetes suggest a correlation between mitochondrial ROS and platelet dysfunction. Therefore, we generated mice with a platelet specific knockout of superoxide dismutase 2 (SOD2-KO) to determine if increased mitochondrial ROS increases platelet activation. SOD2-KO platelets demonstrated decreased SOD2 activity and increased mitochondrial ROS, however total platelet ROS was unchanged. Mitochondrial function and content were maintained in non-stimulated platelets. However SOD2-KO platelets demonstrated decreased mitochondrial function following thrombin stimulation. In vitro platelet activation and spreading was normal and in vivo, deletion of SOD2 did not change tail-bleeding or arterial thrombosis indices. In pathophysiological models mediated by platelet-dependent immune mechanisms such as sepsis and autoimmune inflammatory arthritis, SOD2-KO mice were phenotypically identical to wildtype controls. These data demonstrate that increased mitochondrial ROS does not result in platelet dysfunction.

Keywords

Thrombosis - ROS - platelet physiology - mitochondria

Full Text

References

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