ArticleThe Journal of clinical investigation2009
Persistent eNOS activation secondary to caveolin-1 deficiency induces pulmonary hypertension in mice and humans through PKG nitration.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.
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Who cites it
161 citing papers in PubMed, 1 synthesis or guideline pooled it, 273 citations in OpenAlex.
- New progress in diagnosis and treatment of pulmonary arterial hypertension.Journal of cardiothoracic surgery · 2022Pooled it
- Nitric oxide modulates bone anabolism through regulation of osteoblast glycolysis and differentiation.The Journal of clinical investigation · 2021Trial
- A potential therapeutic role for angiotensin-converting enzyme 2 in human pulmonary arterial hypertension.The European respiratory journal · 2018Trial
- RNF213 in Panvascular Disease: A Molecular Hub Linking Genetic Susceptibility to Systemic Vasculopathy.Biomedicines · 2026Review
- Review
- Cardiovascular Safety of VIAN-c4551, an Antiangiogenic Peptide Derived From Vasoinhibin.Drug development research · 2025Article
- Genetic Manipulation of Caveolin-1 in a Transgenic Mouse Model of Aortic Root Aneurysm: Sex-Dependent Effects on Endothelial and Smooth Muscle Function.International journal of molecular sciences · 2024Article
- ZFYVE21 promotes endothelial nitric oxide signaling and vascular barrier function in the kidney during aging.Kidney international · 2024Article
- The critical roles of caveolin-1 in lung diseases.Frontiers in pharmacology · 2024Review
- The vascular perspective on acute and chronic lung disease.The Journal of clinical investigation · 2023Review
- Metabolic reprogramming, oxidative stress, and pulmonary hypertension.Redox biology · 2023Review
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Cavin-2 loss exacerbates hypoxia-induced pulmonary hypertension with excessive eNOS phosphorylation and protein nitration.Heliyon · 2023Article
- Vascular pathobiology of pulmonary hypertension.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2023Review
- Article
- Dysregulated Smooth Muscle Cell BMPR2-ARRB2 Axis Causes Pulmonary Hypertension.Circulation research · 2023Article
- Interleukin-6 and pulmonary hypertension: from physiopathology to therapy.Frontiers in immunology · 2023Review
- Endothelial PHD2 deficiency induces nitrative stressThe European respiratory journal · 2022Article
- Pathogenic Mechanisms of Pulmonary Arterial Hypertension: Homeostasis Imbalance of Endothelium-Derived Relaxing and Contracting Factors.JACC. Asia · 2022Review
- Mechanosensitive cation currents through TRPC6 and Piezo1 channels in human pulmonary arterial endothelial cells.American journal of physiology. Cell physiology · 2022Article
101 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Pulmonary hypertension (PH) is an unremitting disease defined by a progressive increase in pulmonary vascular resistance leading to right-sided heart failure. Using mice with genetic deletions of caveolin 1 (Cav1) and eNOS (Nos3), we demonstrate here that chronic eNOS activation secondary to loss of caveolin-1 can lead to PH. Consistent with a role for eNOS in the pathogenesis of PH, the pulmonary vascular remodeling and PH phenotype of Cav1-/- mice were absent in Cav1-/-Nos3-/- mice. Further, treatment of Cav1-/- mice with either MnTMPyP (a superoxide scavenger) or l-NAME (a NOS inhibitor) reversed their pulmonary vascular pathology and PH phenotype. Activation of eNOS in Cav1-/- lungs led to the impairment of PKG activity through tyrosine nitration. Moreover, the PH phenotype in Cav1-/- lungs could be rescued by overexpression of PKG-1. The clinical relevance of the data was indicated by the observation that lung tissue from patients with idiopathic pulmonary arterial hypertension demonstrated increased eNOS activation and PKG nitration and reduced caveolin-1 expression. Together, these data show that loss of caveolin-1 leads to hyperactive eNOS and subsequent tyrosine nitration-dependent impairment of PKG activity, which results in PH. Thus, targeting of PKG nitration represents a potential novel therapeutic strategy for the treatment of PH.
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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.