Superoxide Dismutase 2 is dispensable for platelet function

Thromb Haemost. 2017 Oct 5;117(10):1859-1867. doi: 10.1160/TH17-03-0174. Epub 2017 Aug 3.


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: ROS; Thrombosis; mitochondria; platelet physiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis / blood
  • Arthritis / enzymology
  • Arthritis / genetics
  • Blood Platelets / drug effects
  • Blood Platelets / enzymology*
  • Blood Platelets / ultrastructure
  • Carotid Artery Diseases / blood
  • Carotid Artery Diseases / enzymology
  • Carotid Artery Diseases / genetics
  • Disease Models, Animal
  • Genotype
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / enzymology
  • Phenotype
  • Platelet Activation
  • Reactive Oxygen Species / blood
  • Sepsis / blood
  • Sepsis / enzymology
  • Sepsis / genetics
  • Superoxide Dismutase / blood*
  • Superoxide Dismutase / deficiency
  • Superoxide Dismutase / genetics
  • Thrombin / pharmacology
  • Thrombosis / blood
  • Thrombosis / enzymology
  • Thrombosis / genetics
  • Time Factors


  • Reactive Oxygen Species
  • Superoxide Dismutase
  • superoxide dismutase 2
  • Thrombin