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
1  Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA
2  Program in Molecular Medicine University of Utah, Salt Lake City, Utah, USA
3  Fraternal 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
2  Program in Molecular Medicine University of Utah, Salt Lake City, Utah, USA
,
Claudia Araujo
2  Program in Molecular Medicine University of Utah, Salt Lake City, Utah, USA
,
Luc H. Boudreau
4  Department 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
3  Fraternal 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
3  Fraternal 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
2  Program in Molecular Medicine University of Utah, Salt Lake City, Utah, USA
,
Eric Boilard
4  Department 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
2  Program in Molecular Medicine University of Utah, Salt Lake City, Utah, USA
,
E. Dale Abel
2  Program in Molecular Medicine University of Utah, Salt Lake City, Utah, USA
3  Fraternal 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
Financial support: RS work was funded by F32 HL128008–01 and T32 DK 091317. JR was funded by K01 GM 103806. ASW was funded by R01 HL 126547–01. EB’s work is supported by a Canadian Institutes of Health Research Foundation grant (to EB), and is recipient of a salary award from the Canadian Institutes of Health Research (CIHR). LB is a recipient of a fellowship from The Arthritis Society. This work was supported by NIH Grant U54 HL112311 to ASW and EDA who are both established investigators of the American Heart Association.
Further Information

Publication History

Received: 12 March 2017

Accepted after major revision: 11 June 2017

Publication Date:
08 November 2017 (online)

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.