ArticleProceedings of the National Academy of Sciences of the United States of America2020
Unbiased proteomics identifies plasminogen activator inhibitor-1 as a negative regulator of endothelial nitric oxide synthase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
31 citing papers in PubMed, 36 citations in OpenAlex.
- The Association Between Sublingual Microvascular Dysfunction and Plasminogen Activator Inhibitor-One Levels in Chronic Kidney Disease Patients: An Exploratory Study.Microcirculation (New York, N.Y. : 1994) · 2026Article
- Placental plasminogen activator inhibitor 1 is induced by platelet-derived TGF-β independently of TGF-β receptor 3 and is upregulated in preeclampsia.Molecular human reproduction · 2026Article
- Knockdown of endothelial Serpine1 improves stroke recovery by attenuating peri-infarct blood flow and blood-brain barrier disruption.Cell death & disease · 2026Article
- Plasminogen Activator Inhibitor-1 is Internalized by Endothelial Cells via A Pinocytosis-Like Mechanism and Evades Degradation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Review
- PAI-1 is a common driver of aging and diverse diseases.Biomedical journal · 2026Review
- The expanding landscape of adipokines: emerging roles of PAI-1 and vaspin in cardiometabolic diseases.Frontiers in endocrinology · 2026Review
- Microvascular Health as a Key Determinant of Organismal Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Plasminogen activator inhibitor 1 promotes aortic aging-like pathophysiology in humans and mice.The Journal of clinical investigation · 2025Article
- Identifying the role of aging-related genes in intracranial aneurysms through bioinformatics analysis.Chinese neurosurgical journal · 2025Article
- Article
- Role of plasminogen activator inhibitor-1 (PAI-1) in age-related cardiovascular pathophysiology.The journal of cardiovascular aging · 2025Article
- The Recurrence of Venous Thromboembolism in Obstructive Sleep Apnea: A Narrative Review.Canadian respiratory journal · 2025Review
- Subcellular Localization Guides eNOS Function.International journal of molecular sciences · 2024Review
- PAI-1 Regulates the Cytoskeleton and Intrinsic Stiffness of Vascular Smooth Muscle Cells.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Article
- Deconvoluting nitric oxide-protein interactions with spatially resolved multiplex imaging.Chemical science · 2024Article
- Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines.Life (Basel, Switzerland) · 2024Review
- Inducible miR-1224 silences cerebrovascular Serpine1 and restores blood flow to the stroke-affected site of the brain.Molecular therapy. Nucleic acids · 2023Article
- 20-Hydroxyeicosatetraenoic acid (20-HETE): Bioactions, receptors, vascular function, cardiometabolic disease and beyond.Advances in pharmacology (San Diego, Calif.) · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) is a critical mediator of vascular function. eNOS is tightly regulated at various levels, including transcription, co- and posttranslational modifications, and by various protein-protein interactions. Using stable isotope labeling with amino acids in cell culture (SILAC) and mass spectrometry (MS), we identified several eNOS interactors, including the protein plasminogen activator inhibitor-1 (PAI-1). In cultured human umbilical vein endothelial cells (HUVECs), PAI-1 and eNOS colocalize and proximity ligation assays demonstrate a protein-protein interaction between PAI-1 and eNOS. Knockdown of PAI-1 or eNOS eliminates the proximity ligation assay (PLA) signal in endothelial cells. Overexpression of eNOS and HA-tagged PAI-1 in COS7 cells confirmed the colocalization observations in HUVECs. Furthermore, the source of intracellular PAI-1 interacting with eNOS was shown to be endocytosis derived. The interaction between PAI-1 and eNOS is a direct interaction as supported in experiments with purified proteins. Moreover, PAI-1 directly inhibits eNOS activity, reducing NO synthesis, and the knockdown or antagonism of PAI-1 increases NO bioavailability. Taken together, these findings place PAI-1 as a negative regulator of eNOS and disruptions in eNOS-PAI-1 binding promote increases in NO production and enhance vasodilation in vivo.
Indexed as
Identifiers
What OpenQuestion holds
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.