ArticleProceedings of the National Academy of Sciences of the United States of America2021
Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 81 citations in OpenAlex.
- Renin-Angiotensin Signaling and Vascular Function: Insights into Health and Disease.Acta physiologica (Oxford, England) · 2026Review
- Piezo channels in physical field therapy: From mechanotransduction mechanisms to bioelectromagnetic modulation and biomedical applications.Mechanobiology in medicine · 2026Review
- TMEM16A channel signalling microdomains in the regulation of vascular function.The Journal of physiology · 2026Review
- Role of Caveolae and Caveolin in Vascular Physiology and Pathology.Journal of the American Heart Association · 2026Review
- Involvement of Nitric Oxide in TRPV4-Induced Relaxations of Mouse and Human Pulmonary Arteries.Biology · 2026Article
- Toward Specific Detection of Peroxynitrite─Intramolecular Cyclization of Boronobenzylated Pyridinium Probe in Chemical and Cellular Systems.Chemical research in toxicology · 2026Article
- The Potential Role of Calcium Channels in Pulmonary Hypertension.BioMed research international · 2026Review
- Paracrine Smooth Muscle-to-Endothelial Signaling via TNF Elevates Blood Pressure in Obesity.Circulation research · 2025Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Nitrosation of CD36 Regulates Endothelial Function and Serum Lipids.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- TRPV4 activation by TGFβ2 enhances cellular contractility and drives ocular hypertension.eLife · 2025Article
- Imaging Ca2+ Signals in Small Pulmonary Veins at Physiological Intraluminal Pressures.Journal of visualized experiments : JoVE · 2025Article
- Review
- Mechanisms of lung endothelial cell injury and survival in pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Review
- Small molecule probes for peroxynitrite detection.Redox biochemistry and chemistry · 2024Article
- The mitochondrial redistribution of ENOS is regulated by AKT1 and dimer status.Nitric oxide : biology and chemistry · 2024Article
- Transient receptor potential vanilloid 4 channel inhibition attenuates lung ischemia-reperfusion injury in a porcine lung transplant model.The Journal of thoracic and cardiovascular surgery · 2024Article
- Role of transient receptor potential channels in the regulation of vascular tone.Drug discovery today · 2024Review
- Oxidative Stress and Cerebral Vascular Tone: The Role of Reactive Oxygen and Nitrogen Species.International journal of molecular sciences · 2024Review
- Single-Cell RNA-Seq Reveals Coronary Heterogeneity and Identifies CD133Arteriosclerosis, thrombosis, and vascular biology · 2024Article
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
Recent studies have focused on the contribution of capillary endothelial TRPV4 channels to pulmonary pathologies, including lung edema and lung injury. However, in pulmonary hypertension (PH), small pulmonary arteries are the focus of the pathology, and endothelial TRPV4 channels in this crucial anatomy remain unexplored in PH. Here, we provide evidence that TRPV4 channels in endothelial cell caveolae maintain a low pulmonary arterial pressure under normal conditions. Moreover, the activity of caveolar TRPV4 channels is impaired in pulmonary arteries from mouse models of PH and PH patients. In PH, up-regulation of iNOS and NOX1 enzymes at endothelial cell caveolae results in the formation of the oxidant molecule peroxynitrite. Peroxynitrite, in turn, targets the structural protein caveolin-1 to reduce the activity of TRPV4 channels. These results suggest that endothelial caveolin-1-TRPV4 channel signaling lowers pulmonary arterial pressure, and impairment of endothelial caveolin-1-TRPV4 channel signaling contributes to elevated pulmonary arterial pressure in PH. Thus, inhibiting NOX1 or iNOS activity, or lowering endothelial peroxynitrite levels, may represent strategies for restoring vasodilation and pulmonary arterial pressure in PH.
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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.