ArticleBlood2010
Plasminogen activator inhibitor-1 (PAI-1) is cardioprotective in mice by maintaining microvascular integrity and cardiac architecture.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05317806 (Use of Metformin in Prevention and Treatment of Cardiac Fibrosis in PAI-1 Deficient Population), which is not on this map. Cited by 34 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.
Use of Metformin in Prevention and Treatment of Cardiac Fibrosis in PAI-1 Deficient Population
Who cites it
34 citing papers in PubMed, 68 citations in OpenAlex.
- Senkyunolide I and Danshensu in combination ameliorate post-MI myocardial fibrosis by regulatingFrontiers in pharmacology · 2026Article
- PAI-1: A Key Signal at the Crossroads of Stem Cell Differentiation and Senescence.International journal of molecular sciences · 2025Review
- Cardiac Hemorrhage Precedes Hypertension-induced Fibrosis in Plasminogen Activator Inhibitor-1 Deficient Mice.bioRxiv : the preprint server for biology · 2025Article
- Exploring mechanisms of radiation-induced myocardial fibrosis using HMGB1 neutralizing antibody.Journal of molecular histology · 2025Article
- Adipsin improves diabetic hindlimb ischemia through SERPINE1 dependent angiogenesis.Cardiovascular diabetology · 2024Article
- Eosinophils protect pressure overload- and β-adrenoreceptor agonist-induced cardiac hypertrophy.Cardiovascular research · 2023Article
- Lifetime Evaluation of Left Ventricular Structure and Function in Male C57BL/6J Mice after Gamma and Space-Type Radiation Exposure.International journal of molecular sciences · 2023Article
- PAI-1: A Major Player in the Vascular Dysfunction in Obstructive Sleep Apnea?International journal of molecular sciences · 2022Review
- Thrombin in complex with dabigatran can still interact with PAR-1 via exosite-I and instigate loss of vascular integrity.Journal of thrombosis and haemostasis : JTH · 2022Article
- Review
- Loureirin B Alleviates Myocardial Ischemia/Reperfusion Injury via Inhibiting PAI-1/TGF-Evidence-based complementary and alternative medicine : eCAM · 2022Article
- A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to Target?International journal of molecular sciences · 2021Review
- Plasminogen activator inhibitor-1 reduces cardiac fibrosis and promotes M2 macrophage polarization in inflammatory cardiomyopathy.Basic research in cardiology · 2021Article
- Disruption of Abcc6 Transporter in Zebrafish Causes Ocular Calcification and Cardiac Fibrosis.International journal of molecular sciences · 2020Article
- Article
- Myeloperoxidase instigates proinflammatory responses in a cecal ligation and puncture rat model of sepsis.American journal of physiology. Heart and circulatory physiology · 2020Article
- Platelets inhibit apoptotic lung epithelial cell death and protect mice against infection-induced lung injury.Blood advances · 2019Article
- Plasminogen Activator Inhibitor Type I Controls Cardiomyocyte Transforming Growth Factor-β and Cardiac Fibrosis.Circulation · 2017Article
- Overlapping and Divergent Actions of Structurally Distinct Histone Deacetylase Inhibitors in Cardiac Fibroblasts.The Journal of pharmacology and experimental therapeutics · 2017Article
- Plasminogen Activator Inhibitor-1 Protects Mice Against Cardiac Fibrosis by Inhibiting Urokinase-type Plasminogen Activator-mediated Plasminogen Activation.Scientific reports · 2017Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Although the involvement of plasminogen activator inhibitor-1 (PAI-1) in fibrotic diseases is well documented, its role in cardiac fibrosis remains controversial. The goal of this study was to determine the effect of a PAI-1 deficiency (PAI-1(-/-)) on the spontaneous development of cardiac fibrosis. PAI-1(-/-) mice developed pervasive cardiac fibrosis spontaneously with aging, and these mice displayed progressively distorted cardiac architecture and markedly reduced cardiac function. To mechanistically elucidate the role of PAI-1 in cardiac fibrosis, 12-week-old mice were chosen to study the biologic events leading to fibrosis. Although fibrosis was not observed at this early age, PAI-1(-/-) hearts presented with enhanced inflammation, along with increased microvascular permeability and hemorrhage. A potent fibrogenic cytokine, transforming growth factor-beta (TGF-beta), was markedly enhanced in PAI-1(-/-) heart tissue. Furthermore, the expression levels of several relevant proteases associated with tissue remodeling were significantly enhanced in PAI-1(-/-) hearts. These results suggest that PAI-1 is cardioprotective, and functions in maintaining normal microvasculature integrity. Microvascular leakage in PAI-1(-/-) hearts may provoke inflammation, and predispose these mice to cardiac fibrosis. Therefore, a PAI-1 deficiency contributes to the development of cardiac fibrosis by increasing vascular permeability, exacerbating local inflammation, and increasing extracellular matrix remodeling, an environment conducive to accelerated fibrosis.
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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.