ArticleJournal of vascular surgery2012
Impaired fibrinolytic system in ApoE gene-deleted mice with hyperlipidemia augments deep vein thrombosis.
Article in Journal of vascular surgery, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Bioprinted Micro-Clots for Kinetic Analysis of Endothelial Cell-Mediated Fibrinolysis.Advanced healthcare materials · 2025Article
- Regulation of macrophage fibrinolysis during venous thrombus resolution.Thrombosis research · 2024Article
- Immune cell-mediated venous thrombus resolution.Research and practice in thrombosis and haemostasis · 2023Review
- Mechanisms of immunothrombosis and vasculopathy in antiphospholipid syndrome.Seminars in immunopathology · 2022Review
- Resolution of Deep Venous Thrombosis: Proposed Immune Paradigms.International journal of molecular sciences · 2020Review
- Dual-reporter high-throughput screen for small-moleculeThe Journal of biological chemistry · 2019Article
- Fibrinolysis and Inflammation in Venous Thrombus Resolution.Frontiers in immunology · 2019Review
- Update on the electrolytic IVC model for pre-clinical studies of venous thrombosis.Research and practice in thrombosis and haemostasis · 2018Article
- Mouse models of cancer-associated thrombosis.Thrombosis research · 2018Review
- Stenosis of the Inferior Vena Cava: A Murine Model of Deep Vein Thrombosis.Journal of visualized experiments : JoVE · 2017Article
- Animal models of venous thrombosis.Cardiovascular diagnosis and therapy · 2017Review
- Integrating microRNA and messenger RNA expression profiles in a rat model of deep vein thrombosis.International journal of molecular medicine · 2017Article
- Swine Model of Thrombotic Caval Occlusion Created by Autologous Thrombus Injection with Assistance of Intra-caval Net Knitting.Scientific reports · 2015Article
- Article
- Increased 18F-FDG uptake is predictive of rupture in a novel rat abdominal aortic aneurysm rupture model.Annals of surgery · 2015Article
- Enhanced venous thrombus resolution in plasminogen activator inhibitor type-2 deficient mice.Journal of thrombosis and haemostasis : JTH · 2014Article
- Low-molecular-weight heparin modulates vein wall fibrotic response in a plasminogen activator inhibitor 1-dependent manner.Journal of vascular surgery. Venous and lymphatic disorders · 2014Article
- Plasminogen activator-1 overexpression decreases experimental postthrombotic vein wall fibrosis by a non-vitronectin-dependent mechanism.Journal of thrombosis and haemostasis : JTH · 2014Article
- Hyperlipidemia, tissue factor, coagulation, and simvastatin.Trends in cardiovascular medicine · 2014Review
- Anti-hyperlipidemic activity of Rhynchosia nulubilis seeds pickled with brown rice vinegar in mice fed a high-fat diet.Nutrition research and practice · 2013Article
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundHyperlipidemia increases the level of blood plasminogen activator inhibitor-1 (PAI-1) that is responsible for regulating fibrinolysis by inhibiting both urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA). While this fibrinolytic pathway is well known, the role of PAI-1 in venous thrombosis (VT) under hyperlipidemic conditions has not been fully established. We sought to determine the effects of PAI-1 in an in vivo hyperlipidemic model of VT.
methodsC57BL/6 wild-type (WT) mice, apolipoprotein E gene-deleted mice (ApoE-/-) having hyperlipidemia, and PAI-1 gene-deleted (PAI-1-/-) mice were used in this study. Inferior vena cava (IVC) ligation below the level of the renal veins was performed to create a stasis VT. Endpoints included measuring acute thrombosis (day 2) and chronic thrombosis (days 6 and 14). At euthanasia, blood samples were collected for plasmin and PAI-1 activity. In addition, the IVC and its thrombus were evaluated for thrombus weight (TW), u-PA activity, and differential leukocyte count while the vein wall only was analyzed for monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase (MMP) 2, and MMP-9.
resultsCompared to WT at day 2, ApoE-/-mice demonstrated a statistically significant 14% increase in TW (P < .05) and a significant 41% increase in circulating PAI-1 activity (P < .05), while showing a trend of decreased plasmin activity. In addition, TW in ApoE-/-mice was 45% higher than PAI-1-/-mice at day 2 (P < .05), 33% at day 6 (P < .01), and 41% at day 14 (P < .01). ApoE-/-mice exhibited undetectable levels of u-PA in both vein wall and thrombus, compared to WT, at all time points. Also, vein wall MMP-2 was significantly decreased by 64% at day 6 (P < .01) and 58% at day 14 (P < .05). MMP-9 was significantly decreased by 71% at day 2 (P < .01) and 48% at day 6 (P < .01), in ApoE-/-mice compared to WT mice. In addition, in ApoE-/-mice, MCP-1 was significantly decreased by 38% at day 2 (P < .01) and 67% at day 6 (P < .01) vs WT mice. As expected in ApoE mice, following a decrease in MCP-1, monocyte recruitment was significantly decreased at days 6 (P < .01) and 14 (P < .05).
conclusionsA significant increase of circulating PAI-1 levels in hyperlipidemic mice correlated with an early increase in TW due to impaired fibrinolysis. The undetectable levels of u-PA in ApoE-/-mice correlated to a decrease in vein wall MMP-2, MMP-9, MCP-1, and a decrease in monocyte recruitment diminishing thrombus resolution.
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