ArticleThe Journal of clinical investigation2019
Hemodynamic regulation of perivalvular endothelial gene expression prevents deep venous thrombosis.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Prediction and Diagnosis of Venous Thromboembolism Using Artificial Intelligence Approaches: A Systematic Review and Meta-Analysis.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisPooled it
- Next Generation Experimental Models of Venous Physiology and Pathology: Examining Human Relevance in Recapitulating Lower Extremity Flow and Valve Function in New Approach Methods (NAMs).Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Time and architecture: the next two dimensions of microphysiological systems.npj biomedical innovations · 2026Review
- Uniaxial cyclic stretch regulates the expression of thrombomodulin and von Willebrand factor on endothelial cells.Blood vessels, thrombosis & hemostasis · 2025Article
- Molecular Mechanism of Notch Signaling and Macrophages in Deep Vein Thrombosis: A Comprehensive Review.Cell biochemistry and biophysics · 2025Review
- Platelet integrin αIIbβ3 plays a key role in a venous thrombogenesis mouse model.Nature communications · 2024Article
- Persistent Vascular Complications in Long COVID: The Role of ACE2 Deactivation, Microclots, and Uniform Fibrosis.Infectious disease reports · 2024Article
- Venous Thromboembolism: Review of Clinical Challenges, Biology, Assessment, Treatment, and Modeling.Annals of biomedical engineering · 2024Review
- Immune cell-mediated venous thrombus resolution.Research and practice in thrombosis and haemostasis · 2023Review
- Integrated Pathogenesis of Vascular and Cardiac Valve Disease.Circulation research · 2023Article
- PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves.Circulation research · 2023Article
- Three-dimensional morphologic and molecular atlases of nasal vasculature.Nature cardiovascular research · 2023Article
- COVID-19 Associated Vasculitis Confirmed by the Tissues RT-PCR: A Case Series Report.Biomedicines · 2023Article
- Resistance exercise promotes the resolution and recanalization of deep venous thrombosis in a mouse model via SIRT1 upregulation.BMC cardiovascular disorders · 2023Article
- Platelet-Neutrophil Crosstalk in Thrombosis.International journal of molecular sciences · 2023Review
- Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: Multilayered cross-talks in the setting of coinfections and comorbidities.PLoS pathogens · 2023Review
- High risk oral contraceptive hormones do not directly enhance endothelial cell procoagulant activity in vitro.PloS one · 2023Article
- Effect of intermittent pneumatic compression on preventing deep vein thrombosis using microfluidic vein chip.Frontiers in bioengineering and biotechnology · 2023Article
- Venous Thromboembolism in Sepsis: From Bench to Bedside.Biomedicines · 2022Review
- Thrombin spatial distribution determines protein C activation during hemostasis and thrombosis.Blood · 2022Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Deep venous thrombosis (DVT) and secondary pulmonary embolism cause approximately 100,000 deaths per year in the United States. Physical immobility is the most significant risk factor for DVT, but a molecular and cellular basis for this link has not been defined. We found that the endothelial cells surrounding the venous valve, where DVTs originate, express high levels of FOXC2 and PROX1, transcription factors known to be activated by oscillatory shear stress. The perivalvular venous endothelial cells exhibited a powerful antithrombotic phenotype characterized by low levels of the prothrombotic proteins vWF, P-selectin, and ICAM1 and high levels of the antithrombotic proteins thrombomodulin (THBD), endothelial protein C receptor (EPCR), and tissue factor pathway inhibitor (TFPI). The perivalvular antithrombotic phenotype was lost following genetic deletion of FOXC2 or femoral artery ligation to reduce venous flow in mice, and at the site of origin of human DVT associated with fatal pulmonary embolism. Oscillatory blood flow was detected at perivalvular sites in human veins following muscular activity, but not in the immobile state or after activation of an intermittent compression device designed to prevent DVT. These findings support a mechanism of DVT pathogenesis in which loss of muscular activity results in loss of oscillatory shear-dependent transcriptional and antithrombotic phenotypes in perivalvular venous endothelial cells, and suggest that prevention of DVT and pulmonary embolism may be improved by mechanical devices specifically designed to restore perivalvular oscillatory flow.
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Registered trials
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.