ArticleThe Journal of clinical investigation2016
Soluble fms-like tyrosine kinase 1 promotes angiotensin II sensitivity in preeclampsia.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.
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Who cites it
83 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Analysis of the evolution of placental oxidative stress research from a bibliometric perspective.Frontiers in pharmacology · 2024Pooled it
- The effects of sildenafil in maternal and fetal outcomes in pregnancy: A systematic review and meta-analysis.PloS one · 2019Pooled it
- Maternal kidney adaptation and function in pregnancy: review and perspectives.Function (Oxford, England) · 2026Review
- Transforming Preeclampsia Care: Molecular Diagnostics and Therapeutic Innovations.Journal of the American Society of Nephrology : JASN · 2026Review
- Renin-Angiotensin-Aldosterone System in Preeclampsia: Pathophysiological Insights and Links to Vascular Dementia.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Potential impact of nicorandil on the pharmacodynamics of anti-angiogenic agents.Scientific reports · 2026Article
- New Frontiers in the Pathophysiology of Hypertensive Pregnancy Disorders: A Systematic Review of Molecular Insights into Preeclampsia.Current issues in molecular biology · 2026Review
- Maternal age and the predictive performance of the uterine artery pulsatility index for composite adverse perinatal outcomes in late-onset fetal growth restriction: a retrospective cohort study.BMC pregnancy and childbirth · 2026Article
- Impact of Structural Features on the Antioxidant Activity of Organofluorine Diaryl Hydrazones.Molecules (Basel, Switzerland) · 2025Article
- Placenta-Derived Secretions Promote Liver Dysfunction, and Hepatic Serum Amyloid A Mediates Kidney Inflammatory Response in a Preeclampsia-like Mouse Model.International journal of molecular sciences · 2025Article
- Human umbilical cord mesenchymal stem cells improve the pregnancy outcomes of preeclampsia rats via inducing placental angiogenesis.Journal of hypertension · 2025Article
- Sphingosine-1-Phosphate, a Marker of Endothelial Injury and Disease Severity in Preeclampsia.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Association between triglyceride-glucose index in early pregnancy and risk of preeclampsia: a multicenter retrospective cohort study.Lipids in health and disease · 2025Article
- Endothelial METAP1: Tipping the Angiogenic Scales in Postpartum Preeclampsia.Circulation research · 2025Article
- Association Between Systemic Immune-Inflammation Index in Early Pregnancy and Preeclampsia: A Multicenter Cohort Study.Journal of inflammation research · 2025Article
- Gestationally administered RAS modulators reprogram endotoxic cardiovascular and inflammatory profiles in adult male offspring of preeclamptic rats.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Distinct phenotypes in the preeclamptic-like mouse model induced by adenovirus carrying sFlt1 and recombinant sFlt1 protein.European journal of medical research · 2024Article
- Evaluation of vascular peroxidase 1, humanin, MOTS-c and miR-200c expression levels in untreated preeclampsia patients.Molecular biology reports · 2024Article
- Kaempferol modulates Wnt/ β-catenin pathway to alleviate preeclampsia- induced changes and protect renal and ovarian histomorphology.Journal of molecular histology · 2024Article
- Placental Origins of Preeclampsia: Insights from Multi-Omic Studies.International journal of molecular sciences · 2024Review
23 more citing papers are in PubMed but not listed here.
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16 authors.
Funding
Abstract
Preeclampsia is a hypertensive disorder of pregnancy in which patients develop profound sensitivity to vasopressors, such as angiotensin II, and is associated with substantial morbidity for the mother and fetus. Enhanced vasoconstrictor sensitivity and elevations in soluble fms-like tyrosine kinase 1 (sFLT1), a circulating antiangiogenic protein, precede clinical signs and symptoms of preeclampsia. Here, we report that overexpression of sFlt1 in pregnant mice induced angiotensin II sensitivity and hypertension by impairing endothelial nitric oxide synthase (eNOS) phosphorylation and promoting oxidative stress in the vasculature. Administration of the NOS inhibitor l-NAME to pregnant mice recapitulated the angiotensin sensitivity and oxidative stress observed with sFlt1 overexpression. Sildenafil, an FDA-approved phosphodiesterase 5 inhibitor that enhances NO signaling, reversed sFlt1-induced hypertension and angiotensin II sensitivity in the preeclampsia mouse model. Sildenafil treatment also improved uterine blood flow, decreased uterine vascular resistance, and improved fetal weights in comparison with untreated sFlt1-expressing mice. Finally, sFLT1 protein expression inversely correlated with reductions in eNOS phosphorylation in placental tissue of human preeclampsia patients. These data support the concept that endothelial dysfunction due to high circulating sFLT1 may be the primary event leading to enhanced vasoconstrictor sensitivity that is characteristic of preeclampsia and suggest that targeting sFLT1-induced pathways may be an avenue for treating preeclampsia and improving fetal outcomes.
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