Plasma Glutathione Peroxidase Deficiency and Platelet Insensitivity to Nitric Oxide in Children With Familial Stroke
Abstract
Abstract—In a previous report by Freedman et al (J Clin Invest.1996;97:979–987), plasma from 2 brothers with stroke or transient ischemic attack inactivated the antiplatelet effects of nitric oxide (NO), and this effect was found to be a consequence of a deficiency of plasma glutathione peroxidase (GSH-Px). In this study, we attempted to define the generalizability of this deficiency by studying NO-mediated antiplatelet effects in 7 families with familial childhood stroke. Seven families with familial childhood stroke that consecutively presented to a large referral center were included in the study. We monitored ADP-induced aggregation of normal gel-filtered platelets (GFP) in platelet-poor plasma (PPP) from normal individuals and from patients in the presence or absence of an NO donor (S-nitroso–glutathione). Surface P-selectin expression of normal GFP in patients’ PPP was analyzed by flow cytometry after incubation with a P-selectin–specific monoclonal antibody in the presence or absence of the NO donor. We also measured GSH-Px activity in plasmas from family members and normal controls using standard methods. In 6 of 7 families, NO failed to inhibit platelet P-selectin expression and platelet aggregation in PPP from the affected family members and some of their relatives. Of 4 families studied, 3 probands and their corresponding affected parent had 50% decrease in plasma GSH-Px activity. In some patients with childhood stroke, impaired metabolism of reactive oxygen species as a result of reduced GSH-Px activity results in NO insufficiency that affects normal platelet inhibitory mechanisms and predisposes to arterial thrombosis.
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Deficiency of GPx-3 in humans or knockout mice potentiates platelet activation and thrombosis.
“Deficiency of GPx-3 in humans or knockout mice potentiates platelet activation and thrombosis (139, 193, 212).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [212]
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Nitric Oxide Insufficiency, Platelet Activation, and Arterial Thrombosis
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Self-citation
- Authors
- Kenet, G., Freedman, J., Shenkman, B., Regina, E., Brok-Simoni, F., Holzman, F., Vavva, F., Brand, N., Michelson, A., Trolliet, M., Loscalzo, J., & Inbal, A.
- Affiliations
- Boston University (US)
- From the Department of Hematology, Institute of Thrombosis and Hemostasis (G.K., B.S., F.B.-S., F.H., A.I.), Pediatric Neurology Unit (N.B.), Sheba Medical Center, Tel-Hashomer, Sackler Faculty of Medicine, Tel-Aviv University, Israel; and the University of Massachusetts Medical School (A.M.), and Whitaker Cardiovascular Institute and Evans Department of Medicine (J.F., F.V., M.T., J.L.), Boston University School of Medicine, Boston, MA.
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 1999-08
- Volume
- 19
- Issue
- 8
- Pages
- 2017-2023
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W1966551859
- Cited by
- 83
- References
- 45
- Citations by year
- 2025: 2 · 2024: 5 · 2023: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 3 · 2016: 4 · 2015: 4 · 2014: 4 · 2012: 2
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion)
- Funders
- National Institutes of Health (5r01hl053919-03)
- National Heart, Lung, and Blood Institute (HL53919, HL-53993, HL-48743, P01HL048743, R01HL053993)
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- nitric oxide, platelet function, transient ischemic attack, P-selectin, platelet aggregation, ADP-induced aggregation, S-nitrosoglutathione, reactive oxygen species, arterial thrombosis, platelet-poor plasma
- MeSH terms
- Adolescent, Adult, Blood Platelets, Cerebrovascular Disorders, Child, Family Health, Female, Glutathione Peroxidase, Humans, Male, Nitric Oxide, Pedigree
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