ReviewCurrent drug targets2019
Recognition of Plasminogen Activator Inhibitor Type 1 as the Primary Regulator of Fibrinolysis.
Review in Current drug targets, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 84 citations in OpenAlex.
- SERPINE1/PAI-1 in Skeletal Degeneration: A Proposed Context-Dependent Framework for Bone Remodeling Regulation.Calcified tissue international · 2026Review
- The relationship between plasminogen activator inhibitor-1 levels and blood pressure in adolescents with a history of prematurity and/or low birth weight.Pediatric nephrology (Berlin, Germany) · 2026Article
- Venous Thromboembolism and Gut Dysbiosis: Mechanistic Links Between Endotoxemia, Microbial Metabolites, and Thromboinflammation.Nutrients · 2026Review
- Abnormalities of liver sinusoidal endothelial cells in primary biliary cholangitis.World journal of experimental medicine · 2026Article
- Optimizing hemorrhage management in trauma: integrative roles of tranexamic acid and tissue plasminogen activator-augmented viscoelastic testing.Journal of thrombosis and thrombolysis · 2026Review
- The Double-Edged Sword Effect of the Fibrinolytic System in Alzheimer's Disease.Cellular and molecular neurobiology · 2026Review
- The expanding landscape of adipokines: emerging roles of PAI-1 and vaspin in cardiometabolic diseases.Frontiers in endocrinology · 2026Review
- Molecular biomarkers in dialysis-related thrombosis and anticoagulation monitoring: thrombin-antithrombin complex, plasmin-α2-antiplasmin complex, soluble thrombomodulin, tPA/PAI-1/tPAIC, and Anti-Xa.Frontiers in medicine · 2026Review
- Reference Intervals for ROTEM-tPA: Whole-Blood Fibrinolysis Assessment in Healthy Adults.TH open : companion journal to thrombosis and haemostasis · 2026Article
- The immunothrombosis pathway linking pulmonary disease to stroke and neurodegeneration: mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- Differential Characteristics and Comparison Between Long-COVID Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).Biomedicines · 2025Review
- Proteomics of arterial thrombi in acute limb ischemia.Journal of thrombosis and thrombolysis · 2025Article
- Coping Styles and Defense Mechanisms in Healthy Young Adults-Correlations with tPA-BDNF Pathway.Brain sciences · 2025Article
- Challenges and Opportunities of Direct Oral Anticoagulant (DOAC) Therapy in Complex Clinical Scenarios: A Comprehensive Review and Practical Guide.Journal of clinical medicine · 2025Review
- Exploiting the Molecular Properties of Fibrinogen to Control Bleeding Following Vascular Injury.International journal of molecular sciences · 2025Review
- Erbin Regulates Tissue Factors Through Ras/Raf Pathway in Coagulation Disorders in Sepsis.Journal of inflammation research · 2025Article
- Regulation of macrophage fibrinolysis during venous thrombus resolution.Thrombosis research · 2024Article
- Heterogeneity and interplay: the multifaceted role of cancer-associated fibroblasts in the tumor and therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Review
- Unraveling the enigma of long COVID: novel aspects in pathogenesis, diagnosis, and treatment protocols.Inflammopharmacology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The fibrinolytic system consists of a balance between rates of plasminogen activation and fibrin degradation, both of which are finely regulated by spatio-temporal mechanisms. Three distinct inhibitors of the fibrinolytic system that differently regulate these two steps are plasminogen activator inhibitor type-1 (PAI-1), α2-antiplasmin, and thrombin activatable fibrinolysis inhibitor (TAFI). In this review, we focus on the mechanisms by which PAI-1 governs total fibrinolytic activity to provide its essential role in many hemostatic disorders, including fibrinolytic shutdown after trauma. PAI-1 is a member of the serine protease inhibitor (SERPIN) superfamily and inhibits the protease activities of plasminogen activators (PAs) by forming complexes with PAs, thereby regulating fibrinolysis. The major PA in the vasculature is tissue-type PA (tPA) which is secreted from vascular endothelial cells (VECs) as an active enzyme and is retained on the surface of VECs. PAI-1, existing in molar excess to tPA in plasma, regulates the amount of free active tPA in plasma and on the surface of VECs by forming a tPA-PAI-1 complex. Thus, high plasma levels of PAI-1 are directly related to attenuated fibrinolysis and increased risk for thrombosis. Since plasma PAI-1 levels are highly elevated under a variety of pathological conditions, including infection and inflammation, the fibrinolytic potential in plasma and on VECs is readily suppressed to induce fibrinolytic shutdown. A congenital deficiency of PAI-1 in humans, in turn, leads to life-threatening bleeding. These considerations support the contention that PAI-1 is the primary regulator of the initial step of fibrinolysis and governs total fibrinolytic activity.
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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.