Cited by 371Pulmonary Hypertension Research and TreatmentsNitric Oxide and Endothelin EffectsVascular Anomalies and Treatments

Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension

Xu, Weiling, Kaneko, F. Takao, Zheng, Shuo, Comhair, Suzy A. A., Janocha, Allison J., Goggans, Tannishia, Thunnissen, Frederik B. J. M., Farver, Carol +5 more·2004·The FASEB Journal

Abstract

Pulmonary arterial hypertension (PAH), a fatal disease of unknown etiology characterized by impaired regulation of pulmonary hemodynamics and vascular growth, is associated with low levels of pulmonary nitric oxide (NO). Based upon its critical role in mediating vasodilation and cell growth, decrease of NO has been implicated in the pathogenesis of PAH. We evaluated mechanisms for low NO and pulmonary hypertension, including NO synthases (NOS) and factors regulating NOS activity, i.e. the substrate arginine, arginase expression and activity, and endogenous inhibitors of NOS in patients with PAH and healthy controls. PAH lungs had normal NOS I–III expression, but substrate arginine levels were inversely related to pulmonary artery pressures. Activity of arginase, an enzyme that regulates NO biosynthesis through effects on arginine, was higher in PAH serum than in controls, with high‐level arginase expression localized by immunostaining to pulmonary endothelial cells. Further, pulmonary artery endothelial cells derived from PAH lung had higher arginase II expression and produced lower NO than control cells in vitro. Thus, substrate availability affects NOS activity and vasodilation, implicating arginase II and alterations in arginine metabolic pathways in the pathophysiology of PAH.

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Crossref · 10.1096/fj.04-2317fje

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Authors
Xu, W., Kaneko, F. T., Zheng, S., Comhair, S. A. A., Janocha, A. J., Goggans, T., Thunnissen, F. B. J. M., Farver, C., Hazen, S. L., Jennings, C., Dweik, R. A., Arroliga, A. C., & Erzurum, S. C.
Affiliations
  • Cleveland Clinic (US)
  • Department of Pathology Canisius Wihelmina Ziekenhuis Nijmegen The Netherlands
Venue
The FASEB Journal
Publisher
Wiley
Published
2004-09-13
Volume
18
Issue
14
Pages
1746-1748
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
OpenAlex
W2116905957
Cited by
369
References
75
Citations by year
2026: 4 · 2025: 5 · 2024: 14 · 2023: 10 · 2022: 10 · 2021: 18 · 2020: 12 · 2019: 12 · 2018: 16 · 2017: 23 · 2016: 13 · 2015: 17 · 2014: 21 · 2013: 27 · 2012: 13
FWCI
16.61
Type
journal article
Language
en
Open access
closed
Locations
  • The FASEB Journal (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (HL 60917, HL 04265, HL076491)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Genetics › Vascular Anomalies and Treatments
Keywords
pulmonary arterial hypertension, arginase II, nitric oxide production, nitric oxide synthase, arginine metabolism, endothelial cells, pulmonary artery endothelium, vasodilation, pulmonary hypertension pathogenesis, nitric oxide synthase inhibitors
MeSH terms
Arginase, Blood Pressure, Cells, Cultured, Endothelium, Vascular, Humans, Hypertension, Pulmonary, Nitric Oxide, Pulmonary Artery

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