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DOI: 10.1160/TH17-03-0174
Superoxide Dismutase 2 is dispensable for platelet function
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.Publication History
Received:
12 March 2017
Accepted after major revision:
11 June 2017
Publication Date:
08 November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201710/lookinside/thumbnails/10-1160-th17-03-0174-1.jpg)
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.
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