ArticlePloS one2014
SFlt-1 elevates blood pressure by augmenting endothelin-1-mediated vasoconstriction in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 60 citations in OpenAlex.
- Aberrant Uteroplacental and Vascular Signaling and Remodeling by Matrix Metalloproteinases in Pregnancy-Related Hypertension and Preeclampsia.Biomolecules · 2026Review
- Article
- HIF-1α-mediated inhibition of the sFlt-1/sENG/TNF-α pathway promotes angiogenesis to ameliorate pre-eclampsia.Journal of molecular histology · 2025Article
- The effects of purslane consumption on blood pressure in adults: A grading of recommendations, assessment, development, and evaluation-assessed systematic review and meta-analysis of randomized controlled trials.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2025Review
- Hypertension toxicity of VEGFR-TKIs in cancer treatment: incidence, mechanisms, and management strategies.Archives of toxicology · 2025Review
- Identifying mitigating strategies for endothelial cell dysfunction and hypertension in response to VEGF receptor inhibitors.Clinical science (London, England : 1979) · 2024Article
- Endothelin System in Hypertension and Chronic Kidney Disease.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Hypertension in Cardio-Oncology Clinic: an update on etiology, assessment, and management.Cardio-oncology (London, England) · 2023Review
- New Ideas for the Prevention and Treatment of Preeclampsia and Their Molecular Inspirations.International journal of molecular sciences · 2023Review
- Understanding the Role of Chemerin in the Pathophysiology of Pre-Eclampsia.Antioxidants (Basel, Switzerland) · 2023Review
- The effects of alpha lipoic acid (ALA) supplementation on blood pressure in adults: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials.Frontiers in cardiovascular medicine · 2023Review
- The Soluble Fms-like Tyrosine Kinase-1 Contributes to Structural and Functional Changes in Endothelial Cells in Chronic Kidney Disease.International journal of molecular sciences · 2022Article
- VEGF Receptor Inhibitor-Induced Hypertension: Emerging Mechanisms and Clinical Implications.Current oncology reports · 2022Review
- Placental Pathology as a Tool to Identify Women for Postpartum Cardiovascular Risk Screening following Preeclampsia: A Preliminary Investigation.Journal of clinical medicine · 2022Article
- Article
- Placental Ischemia Says "NO" to Proper NOS-Mediated Control of Vascular Tone and Blood Pressure in Preeclampsia.International journal of molecular sciences · 2021Review
- Picotamide inhibits a wide spectrum of agonist-induced smooth muscle contractions in porcine renal interlobar and coronary arteries.Pharmacology research & perspectives · 2021Article
- Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia.Scientific reports · 2021Article
- Soluble syndecan-1 and glycosaminoglycans in preeclamptic and normotensive pregnancies.Scientific reports · 2021Article
- Aspirin for the prevention and treatment of pre-eclampsia: A matter of COX-1 and/or COX-2 inhibition?Basic & clinical pharmacology & toxicology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveScavenging of vascular endothelial growth factor (VEGF) elevates blood pressure (BP) in patients receiving anti-angiogenic therapy. Similarly, inhibition of circulation VEGF by its soluble receptor fms-like tyrosine kinase-1 (sFlt-1) underlies BP elevation in pre-eclampsia. Both phenotypes are characterized by augmented production of endothelin-1 (ET-1), suggesting a role for ET-1 in anti-angiogenic hypertension. We aimed to assess the effect of VEGF inhibition on ET-1-induced contractility and downstream ET-1 signaling. APPROACH AND
resultsMale C57BL/6N mice were treated with either sFlt-1 or vehicle and BP was assessed via tail-cuff. Mean arterial pressure of sFlt-1-treated mice markedly increased compared to vehicle-treated controls (N = 11-12, p<0.05). After sacrifice, carotid and mesenteric arteries were isolated for isometric tension measurements. ET-1-induced contractions were similar in mesenteric arteries of vehicle and sFlt-1-treated mice, but augmented in carotid segments of sFlt-1-treated mice compared to controls (N = 9-10, p<0.05). The increased contraction in carotid segments could be completely abrogated by the cyclooxygenase (COX) inhibitor indomethacin (N = 9-10, p<0.05), indicating heightened prostaglandin-mediated vasoconstriction. This was associated with a shift towards procontractile ETB signaling in sFlt-1-treated mice, possibly explaining the increased ET-1-induced prostaglandin-mediated vasoconstriction. In line with the ex vivo findings, sFlt-1-induced BP elevation could be prevented in vivo by oral treatment with either a high-dose of the COX inhibitor aspirin (N = 7) or with picotamide (N = 9), a dual thromboxane A2 synthase inhibitor and receptor antagonist.
conclusionsVEGF inhibition augments the pressor response to ET-1. The cyclooxygenase-thromboxane signaling route downstream of ET-1 might be a possible target to prevent BP elevation during VEGF inhibition.
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