ArticleProceedings of the National Academy of Sciences of the United States of America2014
Secretion of von Willebrand factor by endothelial cells links sodium to hypercoagulability and thrombosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 105 citations in OpenAlex.
- Contribution of dehydration to END in acute ischemic stroke not mediated via coagulation activation.Brain and behavior · 2019Trial
- Mouse models to study von Willebrand factor in thrombosis: a scoping review.Research and practice in thrombosis and haemostasis · 2026Article
- Dynamic Variability of Sodium and Potassium Predicts Mortality in Critically Ill Patients With Ischemic Stroke: Evidence From Two Critical Care Cohorts.Brain and behavior · 2026Article
- Spontaneous resolution of neonatal umbilical vein thrombosis in the absence of anticoagulant therapy: a case report.Journal of medical case reports · 2026Article
- Mouse models to study von Willebrand factor in inflammation: a scoping review.Intensive care medicine experimental · 2026Review
- Development, internal testing, and external validation of an interpretable machine-learning model for predicting imaging-confirmed in-hospital postoperative deep vein thrombosis in older patients with patellar fractures.BMC medical informatics and decision making · 2026Article
- Neutrophil stalling does not mediate the increase in tau phosphorylation and the cognitive impairment associated with high salt diet.Cardiovascular research · 2025Article
- Association of Plasma Osmolality with Cardiovascular Disease Risk: Evidence from the National Health and Nutrition Examination Survey Database.Arquivos brasileiros de cardiologia · 2025Article
- Assessment of risk factors related to early occurrence of deep vein thrombosis after TBI using nomogram model.Scientific reports · 2025Article
- Electrolyte Levels in Poor Prognosis and Early Neurological Deterioration in Patients With Acute Ischemic Stroke.Journal of clinical hypertension (Greenwich, Conn.) · 2025Article
- Serum sodium within the normal range and its U-shaped relationship with biological aging in U.S. adults.Frontiers in nutrition · 2025Article
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- Multimodal Treatment of a Spontaneously Ruptured Echinococcus Cyst of the Spleen and Its Complications.Case reports in gastrointestinal medicine · 2025Article
- Coronary microthrombi in the failing human heart: the role of von Willebrand factor and PECAM-1.Molecular and cellular biochemistry · 2024Article
- Long-term health outcomes associated with hydration status.Nature reviews. Nephrology · 2024Review
- Hyponatremia, hypernatremia and impairment of functional, psychological and sexual domains.Journal of endocrinological investigation · 2024Article
- SOX17/ETV2 improves the direct reprogramming of adult fibroblasts to endothelial cells.Cell reports methods · 2024Article
- Injectable Shear-Thinning Hydrogels with Sclerosing and Matrix Metalloproteinase Modulatory Properties for the Treatment of Vascular Malformations.Advanced functional materials · 2023Article
- The Importance of Optimal Hydration in Patients with Heart Failure-Not Always Too Much Fluid.Biomedicines · 2023Review
- A new immune disease: systemic hypertension.Clinical kidney journal · 2023Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Hypercoagulability increases risk of thrombi that cause cardiovascular events. Here we identify plasma sodium concentration as a factor that modulates blood coagulability by affecting the production of von Willebrand factor (vWF), a key initiator of the clotting cascade. We find that elevation of salt over a range from the lower end of what is normal in blood to the level of severe hypernatremia reversibly increases vWF mRNA in endothelial cells in culture and the rate of vWF secretion from them. The high NaCl increases expression of tonicity-regulated transcription factor NFAT5 and its binding to promoter of vWF gene, suggesting involvement of hypertonic signaling in vWF up-regulation. To elevate NaCl in vivo, we modeled mild dehydration, subjecting mice to water restriction (WR) by feeding them with gel food containing 30% water. Such WR elevates blood sodium from 145.1 ± 0.5 to 150.2 ± 1.3 mmol/L and activates hypertonic signaling, evidenced from increased expression of NFAT5 in tissues. WR increases vWF mRNA in liver and lung and raises vWF protein in blood. Immunostaining of liver revealed increased production of vWF protein by endothelium and increased number of microthrombi inside capillaries. WR also increases blood level of D-dimer, indicative of ongoing coagulation and thrombolysis. Multivariate regression analysis of clinical data from the Atherosclerosis Risk in Communities Study demonstrated that serum sodium significantly contributes to prediction of plasma vWF and risk of stroke. The results indicate that elevation of extracellular sodium within the physiological range raises vWF sufficiently to increase coagulability and risk of thrombosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.