ArticlePulmonary circulation2015
Vascular endothelial growth factor receptor 3 signaling contributes to angioobliterative pulmonary hypertension.
Article in Pulmonary circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2018Guideline
- Hypoxia Induces Adaptive Lymphangiogenesis via Cd74 and Vegfr3 to Modulate Pulmonary Hypertension.Circulation research · 2026Article
- Understanding the Pathobiology of Pulmonary Hypertension Due to Left Heart Disease.Circulation research · 2022Review
- An inflammatory Signature of Glucose Impairment in Cystic Fibrosis.Journal of inflammation research · 2022Article
- VEGFR3 tyrosine kinase inhibition aggravates cisplatin nephrotoxicity.American journal of physiology. Renal physiology · 2021Article
- Up-Regulation of the Long Noncoding RNA X-Inactive-Specific Transcript and the Sex Bias in Pulmonary Arterial Hypertension.The American journal of pathology · 2021Article
- Endostatin and Vascular Endothelial Growth Factor-ACirculation reports · 2021Article
- MAZ51 Blocks the Tumor Growth of Prostate Cancer by Inhibiting Vascular Endothelial Growth Factor Receptor 3.Frontiers in pharmacology · 2021Article
- Interruption of vascular endothelial growth factor receptor 2 signaling induces a proliferative pulmonary vasculopathy and pulmonary hypertension.Basic research in cardiology · 2020Article
- Heart‑lung crosstalk in pulmonary arterial hypertension following myocardial infarction (Review).International journal of molecular medicine · 2020Review
- The BMP Receptor 2 in Pulmonary Arterial Hypertension: When and Where the Animal Model Matches the Patient.Cells · 2020Article
- Elevated plasma tyrosine kinases VEGF-D and HER4 in heart failure patients decrease after heart transplantation in association with improved haemodynamics.Heart and vessels · 2020Article
- Current Understanding of Circulating Biomarkers in Pulmonary Hypertension Due to Left Heart Disease.Frontiers in medicine · 2020Review
- Highlights from the ERS International Congress 2018: Assembly 13 - Pulmonary Vascular Diseases.ERJ open research · 2019Article
- Vascular Adaptation of the Right Ventricle in Experimental Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2018Article
- Potential lymphangiogenesis therapies: Learning from current antiangiogenesis therapies-A review.Medicinal research reviews · 2018Review
- Research progress on common adverse events caused by targeted therapy for colorectal cancer.Oncology letters · 2018Review
- Drug-induced pulmonary arterial hypertension: a primer for clinicians and scientists.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Endothelial HIF-2α contributes to severe pulmonary hypertension due to endothelial-to-mesenchymal transition.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- The right ventricle and pulmonary hypertension.Heart failure reviews · 2016Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms involved in the development of severe angioobliterative pulmonary arterial hypertension (PAH) are multicellular and complex. Many of the features of human severe PAH, including angioobliteration, lung perivascular inflammation, and right heart failure, are reproduced in the Sugen 5416/chronic hypoxia (SuHx) rat model. Here we address, at first glance, the confusing and paradoxical aspect of the model, namely, that treatment of rats with the antiangiogenic vascular endothelial growth factor (VEGF) receptor 1 and 2 kinase inhibitor, Sugen 5416, when combined with chronic hypoxia, causes angioproliferative pulmonary vascular disease. We postulated that signaling through the unblocked VEGF receptor VEGFR3 (or flt4) could account for some of the pulmonary arteriolar lumen-occluding cell growth. We also considered that Sugen 5416-induced VEGFR1 and VEGFR2 blockade could alter the expression pattern of VEGF isoform proteins. Indeed, in the lungs of SuHx rats we found increased expression of the ligand proteins VEGF-C and VEGF-D as well as enhanced expression of the VEGFR3 protein. In contrast, in the failing right ventricle of SuHx rats there was a profound decrease in the expression of VEGF-B and VEGF-D in addition to the previously described reduction in VEGF-A expression. MAZ51, an inhibitor of VEGFR3 phosphorylation and VEGFR3 signaling, largely prevented the development of angioobliteration in the SuHx model; however, obliterated vessels did not reopen when animals with established PAH were treated with the VEGFR3 inhibitor. Part of the mechanism of vasoobliteration in the SuHx model occurs via VEGFR3. VEGFR1/VEGFR2 inhibition can be initially antiangiogenic by inducing lung vessel endothelial cell apoptosis; however, it can be subsequently angiogenic via VEGF-C and VEGF-D signaling through VEGFR3.
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