Journal article
Nox2 NADPH oxidase is dispensable for platelet activation or arterial thrombosis in mice
Blood advances, Vol.3(8), pp.1272-1284
04/23/2019
DOI: 10.1182/bloodadvances.2018025569
PMCID: PMC6482355
PMID: 30995985
Abstract
Deficiency of the Nox2 (gp91phox) catalytic subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a genetic cause of X-linked chronic granulomatous disease, a condition in which patients are prone to infection resulting from the loss of oxidant production by neutrophils. Some studies have suggested a role for superoxide derived from Nox2 NADPH oxidase in platelet activation and thrombosis, but data are conflicting. Using a rigorous and comprehensive approach, we tested the hypothesis that genetic deficiency of Nox2 attenuates platelet activation and arterial thrombosis. Our study was designed to test the genotype differences within male and female mice. Using chloromethyl-dichlorodihydrofluorescein diacetate, a fluorescent dye, as well as high-performance liquid chromatography analysis with dihydroethidium as a probe to detect intracellular reactive oxygen species (ROS), we observed no genotype differences in ROS levels in platelets. Similarly, there were no genotype-dependent differences in levels of mitochondrial ROS. In addition, we did not observe any genotype-associated differences in platelet activation, adhesion, secretion, or aggregation in male or female mice. Platelets from chronic granulomatous disease patients exhibited similar adhesion and aggregation responses as platelets from healthy subjects. Susceptibility to carotid artery thrombosis in a photochemical injury model was similar in wild-type and Nox2-deficient male or female mice. Our findings indicate that Nox2 NADPH oxidase is not an essential source of platelet ROS or a mediator of platelet activation or arterial thrombosis in large vessels, such as the carotid artery.
Details
- Title: Subtitle
- Nox2 NADPH oxidase is dispensable for platelet activation or arterial thrombosis in mice
- Creators
- Vijay K Sonkar - Department of Internal MedicineRahul Kumar - Department of Internal MedicineMelissa Jensen - Department of Internal MedicineBrett A Wagner - Department of Radiation Oncology, andAnjali A Sharathkumar - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IAFrancis J Miller Jr - Department of Medicine, Duke University, Durham, NCMaryBeth Fasano - Department of Internal MedicineSteven R Lentz - Department of Internal MedicineGarry R Buettner - Department of Radiation Oncology, andSanjana Dayal - Department of Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Blood advances, Vol.3(8), pp.1272-1284
- Publisher
- United States
- DOI
- 10.1182/bloodadvances.2018025569
- PMID
- 30995985
- PMCID
- PMC6482355
- ISSN
- 2473-9529
- eISSN
- 2473-9537
- Grant note
- I01 BX001729 / BLRD VA R01 AG049784 / NIA NIH HHS R01 HL130039 / NHLBI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA169046 / NCI NIH HHS
- Language
- English
- Date published
- 04/23/2019
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Hematology/Oncology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Rheumatology, Allergy, and Immunology; Immunology; Internal Medicine
- Record Identifier
- 9984070319702771
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