ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016
Phosphorylation inactivation of endothelial nitric oxide synthesis in pulmonary arterial hypertension.
Article in American journal of physiology. Lung cellular and molecular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- A Plant-Based Diet Alleviates Molecular Pulmonary Abnormalities in Hypertension.Advances in respiratory medicine · 2025Article
- BK channels are indispensable for endothelial function in small pulmonary arteries.Cell communication and signaling : CCS · 2025Article
- Alterations in Mitochondrial Function in Pulmonary Vascular Diseases.Antioxidants & redox signaling · 2025Article
- Article
- Deacetylation mimetic mutation of mitochondrial SOD2 attenuates ANG II-induced hypertension by protecting against oxidative stress and inflammation.American journal of physiology. Heart and circulatory physiology · 2024Article
- Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: From Bedside to Bench and Back Again.International journal of molecular sciences · 2024Review
- Human Pulmonary Artery Endothelial Cells Increased Glycolysis and Decreased Nitric Oxide Synthase O-GlcNAcylation in Pulmonary Arterial Hypertension.International journal of translational medicine (Basel, Switzerland) · 2024Article
- Metabolic profiling of in vivo right ventricular function and exercise performance in pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Pathophysiology and new advances in pulmonary hypertension.BMJ medicine · 2023Review
- Increased Lung Uric Acid Deteriorates Pulmonary Arterial Hypertension.Journal of the American Heart Association · 2021Article
- Endothelial cells in the pathogenesis of pulmonary arterial hypertension.The European respiratory journal · 2021Review
- Endothelial Dysfunction Driven by Hypoxia-The Influence of Oxygen Deficiency on NO Bioavailability.Biomolecules · 2021Review
- Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension.Antioxidants & redox signaling · 2021Review
- Metabolism in Pulmonary Hypertension.Annual review of physiology · 2021Review
- Novel Experimental Therapies for Treatment of Pulmonary Arterial Hypertension.Journal of experimental pharmacology · 2021Review
- Electrical stimulation of the carotid sinus lowers arterial pressure and improves heart rate variability in L-NAME hypertensive conscious rats.Hypertension research : official journal of the Japanese Society of Hypertension · 2020Article
- A crucial role of endoplasmic reticulum stress in cellular responses during pulmonary arterial hypertension.American journal of translational research · 2020Review
- Integrative proteomics and phosphoproteomics in pulmonary arterial hypertension.Scientific reports · 2019Article
- Repurposing Medications for Treatment of Pulmonary Arterial Hypertension: What's Old Is New Again.Journal of the American Heart Association · 2019Review
- EXPRESS: Gremlin1 blocks vascular endothelial growth factor signalling in the pulmonary microvascular endothelium.Pulmonary circulation · 2018Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The impairment of vasodilator nitric oxide (NO) production is well accepted as a typical marker of endothelial dysfunction in vascular diseases, including in the pathophysiology of pulmonary arterial hypertension (PAH), but the molecular mechanisms accounting for loss of NO production are unknown. We hypothesized that low NO production by pulmonary arterial endothelial cells in PAH is due to inactivation of NO synthase (eNOS) by aberrant phosphorylation of the protein. To test the hypothesis, we evaluated eNOS levels, dimerization, and phosphorylation in the vascular endothelial cells and lungs of patients with PAH compared with controls. In mechanistic studies, eNOS activity in endothelial cells in PAH lungs was found to be inhibited due to phosphorylation at T495. Evidence pointed to greater phosphorylation/activation of protein kinase C (PKC) α and its greater association with eNOS as the source of greater phosphorylation at T495. The presence of greater amounts of pT495-eNOS in plexiform lesions in lungs of patients with PAH confirmed the pathobiological mechanism in vivo. Transfection of the activating mutation of eNOS (T495A/S1177D) restored NO production in PAH cells. Pharmacological blockade of PKC activity by β-blocker also restored NO formation by PAH cells, identifying one mechanism by which β-blockers may benefit PAH and cardiovascular diseases through recovery of endothelial functions.
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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.