The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice
Open accessAbstract
Deep vein thrombosis and pulmonary embolism are major health problems associated with high mortality. Recently, DNA-based neutrophil extracellular traps (NETs) resulting from the release of decondensed chromatin, were found to be part of the thrombus scaffold and to promote coagulation. However, the significance of nuclear decondensation and NET generation in thrombosis is largely unknown. To address this, we adopted a stenosis model of deep vein thrombosis and analyzed venous thrombi in peptidylarginine deiminase 4 (PAD4)-deficient mice that cannot citrullinate histones, a process required for chromatin decondensation and NET formation. Intriguingly, less than 10% of PAD4 −/− mice produced a thrombus 48 h after inferior vena cava stenosis whereas 90% of wild-type mice did. Neutrophils were abundantly present in thrombi formed in both groups, whereas extracellular citrullinated histones were seen only in thrombi from wild-type mice. Bone marrow chimera experiments indicated that PAD4 in hematopoietic cells was the source of the prothrombotic effect in deep vein thrombosis. Thrombosis could be rescued by infusion of wild-type neutrophils, suggesting that neutrophil PAD4 was important and sufficient. Endothelial activation and platelet aggregation were normal in PAD4 −/− mice, as was hemostatic potential determined by bleeding time and platelet plug formation after venous injury. Our results show that PAD4-mediated chromatin decondensation in the neutrophil is crucial for pathological venous thrombosis and present neutrophil activation and PAD4 as potential drug targets for deep vein thrombosis.
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Cites
Neutrophil Extracellular Traps Kill Bacteria
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Novel cell death program leads to neutrophil extracellular traps
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Self-citationExtracellular DNA traps promote thrombosis
Fuchs, T. A., Brill, A., Duerschmied, D., Schatzberg, D., Monestier, M., Myers, D. D., Wrobleski, S. K., Wakefield, T. W., Hartwig, J. H., & Wagner, D. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005743107 · Cited by 2,492
Self-citationvon Brühl, M.-L., Stark, K., Steinhart, A., Chandraratne, S., Konrad, I., Lorenz, M., Khandoga, A., Tirniceriu, A., Coletti, R., Köllnberger, M., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20112322 · Cited by 1,823
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Extracellular histones are major mediators of death in sepsis
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Self-citationPAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps
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Self-citationSaffarzadeh, M., Juenemann, C., Queisser, M. A., Lochnit, G., Barreto, G., Galuska, S. P., Lohmeyer, J., & Preissner, K. T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032366 · Cited by 1,335
Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases
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Cited by
Neutrophil extracellular traps in immunity and disease
Papayannopoulos, V. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.105 · Cited by 3,397
Interplay between inflammation and thrombosis in cardiovascular pathology
Stark, K., & Massberg, S. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00552-1 · Cited by 1,033
Resolution of Inflammation: What Controls Its Onset?
Sugimoto, M. A., Sousa, L. P., Pinho, V., Perretti, M., & Teixeira, M. M. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00160 · Cited by 638
NETosis: Molecular Mechanisms, Role in Physiology and Pathology
Vorobjeva, N. V., & Chernyak, B. V. (2020) · Biochemistry (Moscow) · doi:10.1134/s0006297920100065 · Cited by 559
P-selectin promotes neutrophil extracellular trap formation in mice
Etulain, J., Martinod, K., Wong, S. L., Cifuni, S. M., Schattner, M., & Wagner, D. D. (2015) · Blood · doi:10.1182/blood-2015-01-624023 · Cited by 554
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Metadata
- Authors
- Martinod, K., Demers, M., Fuchs, T. A., Wong, S. L., Brill, A., Gallant, M., Hu, J., Wang, Y., & Wagner, D. D.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2013-05-06
- Volume
- 110
- Issue
- 21
- Pages
- 8674-8679
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2029473544
- Cited by
- 532
- References
- 36
- FWCI
- 15.10
- Type
- journal article
- Language
- en
- Open access
- green
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