ArticleArteriosclerosis, thrombosis, and vascular biology2015
Plasminogen activator inhibitor-1 inhibits angiogenic signaling by uncoupling vascular endothelial growth factor receptor-2-αVβ3 integrin cross talk.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
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- Biomarkers of prognosis and pazopanib response in soft tissue sarcoma: An exploratory analysis.Therapeutic advances in medical oncology · 2026Article
- Cardiac Hemorrhage Precedes Hypertension-induced Fibrosis in Plasminogen Activator Inhibitor-1 Deficient Mice.bioRxiv : the preprint server for biology · 2025Article
- Targeting Plasminogen Activator Inhibitor-1 with a Novel Small Molecule Inhibitor Attenuates Lung Fibrosis.Research square · 2025Article
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- Adipsin improves diabetic hindlimb ischemia through SERPINE1 dependent angiogenesis.Cardiovascular diabetology · 2024Article
- Coagulation factor XI regulates endothelial cell permeability and barrier function in vitro and in vivo.Blood · 2024Article
- Endothelial PDGF-D contributes to neurovascular protection after ischemic stroke by rescuing pericyte functions.Cellular and molecular life sciences : CMLS · 2024Article
- Knockdown of LRCH4 Remodels Tumor Microenvironment Through Inhibiting YAP and TGF-β/Smad Signaling Pathway in Colorectal Cancer.Combinatorial chemistry & high throughput screening · 2024Article
- Non-classical monocytes promote neurovascular repair in cerebral small vessel disease associated with microinfarctions via CX3CR1.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Evolution of p53 pathway-related genes provides insights into anticancer mechanisms of natural longevity in cetaceans.Zoological research · 2023Article
- Novel Function of Cancer Stem Cell Marker ALDH1A3 in Glioblastoma: Pro-Angiogenesis through Paracrine PAI-1 and IL-8.Cancers · 2023Article
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- Adipose Tissue Development Relies on Coordinated Extracellular Matrix Remodeling, Angiogenesis, and Adipogenesis.Biomedicines · 2022Review
- ELTD1 is present in extracellular vesicles derived from endothelial cells as a cleaved extracellular domain which induces in vivo angiogenesis.Journal of extracellular biology · 2022Article
- Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
objectivePlasminogen activator inhibitor-1 (PAI-1) regulates angiogenesis via effects on extracellular matrix proteolysis and cell adhesion. However, no previous study has implicated PAI-1 in controlling vascular endothelial growth factor (VEGF) signaling. We tested the hypothesis that PAI-1 downregulates VEGF receptor-2 (VEGFR-2) activation by inhibiting a vitronectin-dependent cooperative binding interaction between VEGFR-2 and αVβ3. APPROACH AND
resultsWe studied effects of PAI-1 on VEGF signaling in human umbilical vein endothelial cells. PAI-1 inhibited VEGF-induced phosphorylation of VEGFR-2 in human umbilical vein endothelial cells grown on vitronectin, but not on fibronectin or collagen. PAI-1 inhibited the binding of VEGFR-2 to β3 integrin, VEGFR-2 endocytosis, and intracellular signaling pathways downstream of VEGFR-2. The anti-VEGF effect of PAI-1 was mediated by 2 distinct pathways, one requiring binding to vitronectin and another requiring binding to very low-density lipoprotein receptor. PAI-1 inhibited VEGF-induced angiogenesis in vitro and in vivo, and pharmacological inhibition of PAI-1 promoted collateral arteriole development and recovery of hindlimb perfusion after femoral artery interruption.
conclusionsPAI-1 inhibits activation of VEGFR-2 by VEGF by disrupting a vitronectin-dependent proangiogenic binding interaction involving αVβ3 and VEGFR-2. These results broaden our understanding of the roles of PAI-1, vitronectin, and endocytic receptors in regulating VEGFR-2 activation and suggest novel therapeutic strategies for regulating VEGF signaling.
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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.