ArticleDNA and cell biology2009
Endothelin-1 impairs nitric oxide signaling in endothelial cells through a protein kinase Cdelta-dependent activation of STAT3 and decreased endothelial nitric oxide synthase expression.
Article in DNA and cell biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Activin A-Endothelin-1 Axis Governs Pulmonary Vascular Remodeling: Mechanistic Basis for Emerging Therapies in PAH.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Article
- Endothelial dysfunction in middle-aged and older men with low testosterone is associated with elevated circulating endothelin-1.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- The effect of endothelin a receptor inhibition and biological sex on cutaneous microvascular function in non-Hispanic Black and White young adults.Physiological reports · 2024Article
- Crosstalk mechanisms between glomerular endothelial cells and podocytes in renal diseases and kidney transplantation.Kidney research and clinical practice · 2024Article
- Differential roles of eNOS in late effects of VEGF-A on hyperpermeability in different types of endothelial cells.Scientific reports · 2023Article
- PKCδ regulates the vascular biology in diabetic atherosclerosis.Cell communication and signaling : CCS · 2023Review
- Endothelin A receptor inhibition increases nitric oxide-dependent vasodilation independent of superoxide in non-Hispanic Black young adults.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
- Molecular pathways that drive diabetic kidney disease.The Journal of clinical investigation · 2023Review
- The role of fibrinolysis in the development of prediabetes-associated coronary heart disease: a focus on the plasminogen activator inhibitor -1 and its potential use as a predictive marker in diet-induced prediabetes.Frontiers in nutrition · 2023Article
- β-PIX cooperates with GIT1 to regulate endothelial nitric oxide synthase in sinusoidal endothelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Role of Endothelial STAT3 in Cerebrovascular Function and Protection from Ischemic Brain Injury.International journal of molecular sciences · 2022Article
- TheInternational journal of environmental research and public health · 2022Article
- Signal Transduction during Metabolic and Inflammatory Reprogramming in Pulmonary Vascular Remodeling.International journal of molecular sciences · 2022Review
- The Role of JAK/STAT Molecular Pathway in Vascular Remodeling Associated with Pulmonary Hypertension.International journal of molecular sciences · 2021Review
- New Therapeutic Insight into the Effect of Ma Huang Tang on Blood Pressure and Renal Dysfunction in the L-NAME-Induced Hypertension.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- S-Nitroso-L-Cysteine Ameliorated Pulmonary Hypertension in the MCT-Induced Rats through Anti-ROS and Anti-Inflammatory Pathways.Oxidative medicine and cellular longevity · 2021Article
- Therapeutic Potential of Quercetin to Alleviate Endothelial Dysfunction in Age-Related Cardiovascular Diseases.Frontiers in cardiovascular medicine · 2021Review
- ET-1 as a Sex-Specific Mechanism Impacting Age-Related Changes in Vascular Function.Frontiers in aging · 2021Review
- Endothelin-1-induced endothelial microvesicles impair endothelial cell function.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In an ovine model of persistent pulmonary hypertension of the newborn (PPHN), endothelin-1 (ET-1) expression is increased, while endothelial nitric oxide synthase (eNOS) expression is decreased. However, the molecular mechanisms by which ET-1 attenuates eNOS expression in endothelial cells are not completely understood. Thus, the goal of this study was to determine if the overexpression of ET-1 decreases eNOS expression in pulmonary arterial endothelial cells isolated from fetal lambs. To increase the ET-1 expression, cells were transfected with a plasmid coding for Prepro-ET-1, a precursor of ET-1. After overexpression of Prepro-ET-1, ET-1 levels in the culture medium were significantly increased (control = 805.3 +/- 69.8; Prepro-ET-1 overexpression = 1351 +/- 127.9). eNOS promoter activity, protein levels, and NO generation were all significantly decreased by the overexpression of Prepro-ET-1. The decrease in transcription correlated with increased activity of protein kinase Cdelta (PKCdelta) and STAT3. Further, DNA binding activity of STAT3 was also increased by Prepro-ET-1 overexpression. The increase in STAT3 activity and decrease in eNOS promoter activity were inhibited by the overexpression of dominant negative mutants of PKCdelta or STAT3. Further, a 2 bp mutation in the STAT3 binding site in the eNOS promoter inhibited STAT3 binding and led to enhanced promoter activity in the presence of Prepro-ET-1 overexpression. In conclusion, ET-1 secretion is increased by Prepro-ET-1 overexpression. This results in activation of PKCdelta, which phosphorylates STAT3, increasing its binding to the eNOS promoter. This in turn decreases eNOS promoter activity, protein levels, and NO production. Thus, ET-1 can reduce eNOS expression and NO generation in fetal pulmonary artery endothelial cells through PKCdelta-mediated activation of STAT3.
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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.