Journal article
Loss of Endogenous Nox2-NADPH Oxidase does not Prevent Age-induced Platelet Activation and Arterial Thrombosis in Mice
Research and practice in thrombosis and haemostasis, Vol.8(7), 102597
10/2024
DOI: 10.1016/j.rpth.2024.102597
PMCID: PMC11585761
PMID: 39582807
Abstract
Reactive oxygen species (ROS) are known to contribute to platelet hyperactivation and thrombosis during aging, however, mechanistic contribution of the specific oxidative pathway remains elusive. We hypothesized that during aging, endogenous Nox2-NADPH oxidase contributes to platelet ROS accumulation and that loss of Nox2 will protect from platelet activation and thrombosis.
We studied littermates of Nox2-knockout (Nox2-KO) and wild type (Nox2-WT) mice at young (3-4 months) and old (18-20 months) age. Within platelets, we examined expression of subunits of NADPH oxidase and enzyme activity, oxidant levels, activation markers, aggregation, and secretion. We also assessed susceptibility to in vivo thrombosis in two experimental models.
While aged Nox2-WT mice displayed increased mRNA levels for Nox2, aged Nox2-KO mice showed increase in Nox4 mRNA. However, neither the protein levels of several subunits, nor the activity of NADPH oxidase were found altered with age or genotype. Both aged Nox2-WT and aged Nox2-KO mice exhibited similar enhancement in levels of platelet-oxidants, granule release, αIIbβ3 activation, annexin V binding, aggregation and secretion, and a greater susceptibility to platelet-induced pulmonary thrombosis compared to young mice. In a photochemical injury model, adoptive transfer of platelets from aged Nox2-WT or Nox2-KO mice to the aged host mice resulted in similar time to develop occlusive thrombus in the carotid artery. These findings suggest that loss of endogenous Nox2 does not protect against age-related platelet activation and arterial thrombosis in mice.
We conclude that Nox2 is not an essential mediator of prothrombotic effects associated with aging.
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1.Age-induced thrombosis is known to be mediated via reactive oxygen species (ROS).2.We tested if Nox2 contributes to ROS-mediated prothrombotic phenotype during aging.3.Loss of Nox2 does not inhibit platelet-ROS, -activation or thrombosis in aged mice.4.Targeting of mediators other than Nox2 should be considered to limit age-induced thrombosis.
Details
- Title: Subtitle
- Loss of Endogenous Nox2-NADPH Oxidase does not Prevent Age-induced Platelet Activation and Arterial Thrombosis in Mice
- Creators
- Azaj Ahmed - Department of Internal MedicineGokul Patil - Department of Internal MedicineVijay K. Sonkar - University of IowaMelissa Jensen - Department of Internal MedicineJennifer Streeter - Department of Internal MedicineSanjana Dayal - Department of Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Research and practice in thrombosis and haemostasis, Vol.8(7), 102597
- DOI
- 10.1016/j.rpth.2024.102597
- PMID
- 39582807
- PMCID
- PMC11585761
- NLM abbreviation
- Res Pract Thromb Haemost
- ISSN
- 2475-0379
- eISSN
- 2475-0379
- Publisher
- Elsevier Inc
- Grant note
- American Heart Association: 24POST1195019, 23IPA1054531 National Institutes of Health: AG049784, AI162778, HL168630 Office of Research and Development and Department of Veterans Affairs: I01CX001932
This work was possible through funding from American Heart Association 24POST1195019 https://doi.org/10.58275/AHA.24POST1195 019.pc.gr.190825 to A.A. and 23IPA1054531 to J.S., from National Institutes of Health AG049784, AI162778, and HL168630, and Office of Research and Development and Department of Veterans Affairs I01CX001932 to S.D.
- Language
- English
- Electronic publication date
- 10/2024
- Date published
- 10/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Iowa Neuroscience Institute; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984738440702771
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