ArticleJournal of the American Heart Association2022
DNase 1 Protects From Increased Thrombin Generation and Venous Thrombosis During Aging: Cross-Sectional Study in Mice and Humans.
Article in Journal of the American Heart Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Circulating cfdna: A novel biomarker for preventing early recurrence in ischemic stroke.Journal of thrombosis and thrombolysis · 2026Review
- Article
- The Mechanism and Potential Therapeutic Strategies of Vascular Aging.Aging medicine (Milton (N.S.W)) · 2025Review
- Elevated tissue factor pathway inhibitor delays thrombin generation in COVID-19 but is not associated with clinical outcomes.Blood vessels, thrombosis & hemostasis · 2025Article
- Tandem ssDNA in neutrophil extracellular traps binds thrombin and regulates immunothrombosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The crucial role of neutrophil extracellular traps and IL-17 signaling in indomethacin-induced gastric injury in mice.Scientific reports · 2025Article
- The Fifth Annual Symposium of the Midwest Aging Consortium.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Effects of exogenous deoxyribonuclease I in collagen antibody-induced arthritis.Journal of inflammation (London, England) · 2024Article
- Extracellular histones: a unifying mechanism driving platelet-dependent extracellular vesicle release and thrombus formation in COVID-19.Journal of thrombosis and haemostasis : JTH · 2024Article
- Review
- Platelet factor 4 limits neutrophil extracellular trap- and cell-free DNA-induced thrombogenicity and endothelial injury.JCI insight · 2023Article
- Comparative Thrombin Generation in Animal Plasma: Sensitivity to Human Factor XIa and Tissue Factor.International journal of molecular sciences · 2023Article
- The effect of neutrophil extracellular traps in venous thrombosis.Thrombosis journal · 2023Review
- Poststroke venous thromboembolism and neutrophil activation: an illustrated review.Research and practice in thrombosis and haemostasis · 2023Article
- Platelet-Neutrophil Crosstalk in Thrombosis.International journal of molecular sciences · 2023Review
- Recent Advances on the Molecular Mechanism and Clinical Trials of Venous Thromboembolism.Journal of inflammation research · 2023Review
- Neutrophil extracellular traps mediate deep vein thrombosis: from mechanism to therapy.Frontiers in immunology · 2023Review
- Article
- Immunothrombosis and the Role of Platelets in Venous Thromboembolic Diseases.International journal of molecular sciences · 2022Review
- The diagnostic potential of novel biomarkers of hypertension in men.Archives of medical science : AMS · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Background Human aging is associated with increased risk of thrombosis, but the mechanisms are poorly defined. We hypothesized that aging induces peroxide-dependent release of neutrophil extracellular traps that contribute to thrombin generation and thrombosis. Methods and Results We studied C57BL6J mice and littermates of glutathione peroxidase-1 transgenic and wild-type mice at young (4 month) and old (20 month) ages and a healthy cohort of young (18-39 years) or middle-aged/older (50-72 years) humans. In plasma, we measured thrombin generation potential and components of neutrophil extracellular traps (cell-free DNA and citrullinated histone). Aged wild-type mice displayed a significant increase in thrombin generation that was decreased in aged glutathione peroxidase-1 transgenic mice. Both aged wild-type and aged glutathione peroxidase-1 transgenic mice demonstrated similar elevation of plasma cell-free DNA compared with young mice. In contrast, plasma levels of citrullinated histone were not altered with age or genotype. Release of neutrophil extracellular traps from neutrophils in vitro was also similar between young and aged wild-type or glutathione peroxidase-1 transgenic mice. Treatment of plasma or mice with DNase 1 decreased age-associated increases in thrombin generation, and DNase 1 treatment blocked the development of experimental venous thrombi in aged C57BL6J mice. Similarly, thrombin generation potential and plasma cell-free DNA, but not citrullinated histone, were higher in middle-aged/older humans, and treatment of plasma with DNase 1 reversed the increase in thrombin generation. Conclusions We conclude that DNase 1 limits thrombin generation and protects from venous thrombosis during aging, likely by hydrolyzing cell-free DNA.
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Registered trials
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