ArticleProceedings of the National Academy of Sciences of the United States of America2012
Endostatin lowers blood pressure via nitric oxide and prevents hypertension associated with VEGF inhibition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 49 citations in OpenAlex.
- Effect of oral niacin on central retinal vein occlusion.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2017Trial
- Hypertension and Circulating Cytokines and Angiogenic Factors in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma Treated With Sunitinib: Results From a Phase II Trial.The oncologist · 2015Trial
- Observational
- Orthostatic hypotension is associated with higher levels of circulating endostatin.European heart journal open · 2024Article
- Circulatory endostatin level and risk of cardiovascular events in patients with end-stage renal disease on hemodialysis.Kidney research and clinical practice · 2024Article
- Case report: Successful therapy with recombinant human vascular endostatin in an elderly man with colon telangiectasia and idiopathic thrombocytopenic purpura.Frontiers in medicine · 2024Article
- Endostatin and Cystatin C as Potential Biomarkers for Early Prediction of Preeclampsia.ACS omega · 2023Article
- Cellular and molecular mechanisms in vascular repair after traumatic brain injury: a narrative review.Burns & trauma · 2023Review
- Knockdown of miR-423-5p simultaneously upgrades the eNOS and VEGFa pathways in ADSCs and improves erectile function in diabetic rats.Journal of cellular and molecular medicine · 2021Article
- Review
- Efficacy and safety of recombinant human endostatin combined with radiotherapy or chemoradiotherapy in patients with locally advanced non-small cell lung cancer: a pooled analysis.Radiation oncology (London, England) · 2020Article
- Vascular endothelium dysfunction: a conservative target in metabolic disorders.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Review
- Endostatin Stimulates Proliferation and Migration of Myofibroblasts Isolated from Myocardial Infarction Model Rats.International journal of molecular sciences · 2018Article
- Nitric oxide synthesis-promoting effects of valsartan in human umbilical vein endothelial cells via the Akt/adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway.Bosnian journal of basic medical sciences · 2017Article
- Anti-VEGF-Induced Hypertension: a Review of Pathophysiology and Treatment Options.Current treatment options in cardiovascular medicine · 2016Article
- Minicircle DNA-mediated endothelial nitric oxide synthase gene transfer enhances angiogenic responses of bone marrow-derived mesenchymal stem cells.Stem cell research & therapy · 2016Article
- Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications.Biochimica et biophysica acta · 2015Review
- Associations of Endothelial System Genes With Blood Pressure Changes and Hypertension Incidence: The GenSalt Study.American journal of hypertension · 2015Article
- Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of Angiogenesis.Journal of ophthalmology · 2015Article
- Evaluation of a novel blood pressure scoring method and its association with clinical response in cancer patients treated with anti-vascular endothelial growth factor therapy.Investigational new drugs · 2014Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Antiangiogenesis therapy has become a vital part of the armamentarium against cancer. Hypertension is a dose-limiting toxicity for VEGF inhibitors. Thus, there is a pressing need to address the associated adverse events so these agents can be better used. The hypertension may be mediated by reduced NO bioavailability resulting from VEGF inhibition. We proposed that the hypertension may be prevented by coadministration with endostatin (ES), an endogenous angiogenesis inhibitor with antitumor effects shown to increase endothelial NO production in vitro. We determined that Fc-conjugated ES promoted NO production in endothelial and smooth muscle cells. ES also lowered blood pressure in normotensive mice and prevented hypertension induced by anti-VEGF antibodies. This effect was associated with higher circulating nitrate levels and was absent in eNOS-knockout mice, implicating a NO-mediated mechanism. Retrospective study of patients treated with ES in a clinical trial revealed a small but significant reduction in blood pressure, suggesting that the findings may translate to the clinic. Coadministration of ES with VEGF inhibitors may offer a unique strategy to prevent drug-related hypertension and enhance antiangiogenic tumor suppression.
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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.