ArticleBlood2020
A high-fat diet delays plasmin generation in a thrombomodulin-dependent manner in mice.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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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
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Assays to quantify fibrinolysis: strengths and limitations. Communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee on fibrinolysis.Journal of thrombosis and haemostasis : JTH · 2023Guideline
- Deep learning-guided high-throughput screening and molecular dynamics simulations facilitate the discovery of potential FXIIa inhibitors.Journal of molecular modeling · 2026Article
- Myrtle berry juice improves hematological parameters and alleviates oxidative stress and inflammation in the myocardium of rats fed a high-fat diet: A combined in vivo and in silico investigation.Journal of the science of food and agriculture · 2026Article
- A novel biosensor for measuring plasmin activity.Research and practice in thrombosis and haemostasis · 2026Article
- Urokinase Plasminogen Activator Deficiency Delays the Development of Obesity and Metabolic Sequelae.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Adaption of the plasmin generation assay to enhance sensitivity to plasminogen activator inhibitor-1 and establishment of sex-specific reference values in human plasma.Research and practice in thrombosis and haemostasis · 2026Article
- Plasmin Generation Kinetics Reveal a Hyperfibrinolytic Phenotype in Patients with Pancreatic Ductal Adenocarcinoma.TH open : companion journal to thrombosis and haemostasis · 2026Article
- Article
- Plasminogen activation and plasmin activity are not necessary to prevent venous thrombosis/thromboembolism.Blood · 2025Observational
- Extracellular Vesicles Profile and Risk of Venous Thromboembolism in Patients with Diffuse Large B-Cell Lymphoma.International journal of molecular sciences · 2025Article
- Impact of soluble thrombomodulin and activated protein C on dynamic hemostatic function in trauma: a focus on thrombin generation and clot lysis.Haematologica · 2025Article
- Venous thrombosis and obesity: from clinical needs to therapeutic challenges.Internal and emergency medicine · 2025Review
- Plasmin generation analysis in patients with bleeding disorder of unknown cause.Blood advances · 2024Article
- Hepatocyte-independent PAR1-biased signaling controls liver pathology in experimental obesity.Journal of thrombosis and haemostasis : JTH · 2024Article
- The thrombin receptor PAR4 supports visceral adipose tissue inflammation.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Trauma-induced dysfibrinogenemia: the von Clauss assay does not accurately measure fibrinogen levels after injury.Blood vessels, thrombosis & hemostasis · 2024Article
- Investigation of thrombin concentration at the time of clot formation in simultaneous thrombin and fibrin generation assays.Scientific reports · 2024Article
- Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A.Science translational medicine · 2024Article
- Article
- Plasminogen deficiency suppresses pancreatic ductal adenocarcinoma disease progression.Molecular oncology · 2024Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Obesity is a prevalent prothrombotic risk factor marked by enhanced fibrin formation and suppressed fibrinolysis. Fibrin both promotes thrombotic events and drives obesity pathophysiology, but a lack of essential analytical tools has left fibrinolytic mechanisms affected by obesity poorly defined. Using a plasmin-specific fluorogenic substrate, we developed a plasmin generation (PG) assay for mouse plasma that is sensitive to tissue plasminogen activator, α2-antiplasmin, active plasminogen activator inhibitor (PAI-1), and fibrin formation, but not fibrin crosslinking. Compared with plasmas from mice fed a control diet, plasmas from mice fed a high-fat diet (HFD) showed delayed PG and reduced PG velocity. Concurrent to impaired PG, HFD also enhanced thrombin generation (TG). The collective impact of abnormal TG and PG in HFD-fed mice produced normal fibrin formation kinetics but delayed fibrinolysis. Functional and proteomic analyses determined that delayed PG in HFD-fed mice was not due to altered levels of plasminogen, α2-antiplasmin, or fibrinogen. Changes in PG were also not explained by elevated PAI-1 because active PAI-1 concentrations required to inhibit the PG assay were 100-fold higher than circulating concentrations in mice. HFD-fed mice had increased circulating thrombomodulin, and inhibiting thrombomodulin or thrombin-activatable fibrinolysis inhibitor (TAFI) normalized PG, revealing a thrombomodulin- and TAFI-dependent antifibrinolytic mechanism. Integrating kinetic parameters to calculate the metric of TG/PG ratio revealed a quantifiable net shift toward a prothrombotic phenotype in HFD-fed mice. Integrating TG and PG measurements may define a prothrombotic risk factor in diet-induced obesity.
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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.