ArticlePloS one2012
A heat-shock protein axis regulates VEGFR2 proteolysis, blood vessel development and repair.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 62 citations in OpenAlex.
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- Non-pharmacological interventions for vascular health and the role of the endothelium.European journal of applied physiology · 2022Review
- An open-label, crossover study to compare different formulations and evaluate effect of food on pharmacokinetics of pimitespib in patients with advanced solid tumors.Investigational new drugs · 2022Article
- Novel Drugs with High Efficacy against Tumor Angiogenesis.International journal of molecular sciences · 2022Review
- A novel atmospheric-pressure air plasma jet for wound healing.International wound journal · 2022Article
- Co-Inhibition of P-gp and Hsp90 by an Isatin-Derived Compound Contributes to the Increase of the Chemosensitivity of MCF7/ADR-Resistant Cells to Doxorubicin.Molecules (Basel, Switzerland) · 2021Article
- Article
- Phase 1 study of the HSP90 inhibitor onalespib in combination with AT7519, a pan-CDK inhibitor, in patients with advanced solid tumors.Cancer chemotherapy and pharmacology · 2020Article
- Heat Shock Proteins Are Essential Components in Transformation and Tumor Progression: Cancer Cell Intrinsic Pathways and Beyond.International journal of molecular sciences · 2019Review
- Exosomes and Hepatocellular Carcinoma: From Bench to Bedside.International journal of molecular sciences · 2019Review
- Cardiovascular Effects of PCB 126 (3,3',4,4',5-Pentachlorobiphenyl) in Zebrafish Embryos and Impact of Co-Exposure to Redox Modulating Chemicals.International journal of molecular sciences · 2019Article
- Imaging of angiogenesis of human umbilical vein endothelial cells by uptake of exosomes secreted from hepatocellular carcinoma cells.Scientific reports · 2018Article
- Micro RNAs are involved in activation of epicardium during zebrafish heart regeneration.Cell death discovery · 2018Article
- Cross-Adaptation: Heat and Cold Adaptation to Improve Physiological and Cellular Responses to Hypoxia.Sports medicine (Auckland, N.Z.) · 2017Review
- A pyrrole-based natural small molecule mitigates HSP90 expression in MDA-MB-231 cells and inhibits tumor angiogenesis in mice by inactivating HSF-1.Cell stress & chaperones · 2017Article
- Dynasore impairs VEGFR2 signalling in an endocytosis-independent manner.Scientific reports · 2017Article
- Heat and Hypoxic Acclimation Increase Monocyte Heat Shock Protein 72 but Do Not Attenuate Inflammation following Hypoxic Exercise.Frontiers in physiology · 2017Article
- Constitutive Endocytosis of VEGFR2 Protects the Receptor against Shedding.The Journal of biological chemistry · 2016Article
- VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis.Biology open · 2016Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Vascular endothelial growth factor A (VEGF-A) binds to the VEGFR2 receptor tyrosine kinase, regulating endothelial function, vascular physiology and angiogenesis. However, the mechanism underlying VEGFR2 turnover and degradation in this response is unclear. Here, we tested a role for heat-shock proteins in regulating the presentation of VEGFR2 to a degradative pathway. Pharmacological inhibition of HSP90 stimulated VEGFR2 degradation in primary endothelial cells and blocked VEGF-A-stimulated intracellular signaling via VEGFR2. HSP90 inhibition stimulated the formation of a VEGFR2-HSP70 complex. Clathrin-mediated VEGFR2 endocytosis is required for this HSP-linked degradative pathway for targeting VEGFR2 to the endosome-lysosome system. HSP90 perturbation selectively inhibited VEGF-A-stimulated human endothelial cell migration in vitro. A mouse femoral artery model showed that HSP90 inhibition also blocked blood vessel repair in vivo consistent with decreased endothelial regeneration. Depletion of either HSP70 or HSP90 caused defects in blood vessel formation in a transgenic zebrafish model. We conclude that perturbation of the HSP70-HSP90 heat-shock protein axis stimulates degradation of endothelial VEGFR2 and modulates VEGF-A-stimulated intracellular signaling, endothelial cell migration, blood vessel development and repair.
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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.