Cited by 57Rheumatoid Arthritis Research and TherapiesRenin-Angiotensin System StudiesOsteoarthritis Treatment and Mechanisms

Angiotensin converting enzyme in human synovium: increased stromal [125I]351A binding in rheumatoid arthritis

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Walsh, David Andrew, Catravas, John, Wharton, John·2000·Annals of the Rheumatic Diseases

Abstract

Objective To determine whether tissue angiotensin converting enzyme (ACE) is increased in synovia from patients with rheumatoid arthritis, osteoarthritis or chondromalacia patellae.Methods Sections of synovia from patients with rheumatoid arthritis (n = 7), osteoarthritis (n = 7) or chondromalacia patellae (n = 6) were tested for immunoreactivity for ACE, and for binding of the ACE inhibitor [(125)I]351A. The amount of ACE was measured with computer assisted image analysis as the proportion of synovial section area occupied by ACE-immunoreactive cells, and the density of [(125)I]351A binding.Results [(125)I]351A binding sites had characteristics of ACE and colocalised with ACE-like immunoreactivity to microvascular endothelium and fibroblast-like stromal cells in inflamed and non-inflamed human synovium. Stromal [(125)I]351A binding densities (B(eq)) and the fraction of synovial section area occupied by ACE-immunoreactivity (fractional area) were higher in synovia from patients with rheumatoid arthritis (B(eq) 28 amol/mm(2), fractional area 0.21) than from those with osteoarthritis (B(eq) 9 amol/mm(2), fractional area 0.10) or chondromalacia patellae (B(eq) 9 amol/mm(2), fractional area 0.09)(p < 0.05). Density of [(125)I]351A binding to stroma was similar to that to blood vessels in rheumatoid arthritis, but less dense than vascular binding in chondromalacia patellae and osteoarthritis. Increases in [(125)I]351A binding densities were attributable to increases in the numbers of binding sites, and were consistent with an increase in the density of ACE bearing stromal cells.Conclusion ACE is upregulated in synovial stroma in rheumatoid arthritis. Increased tissue ACE may result in increased local generation of the vasoconstrictor and mitogenic peptide angiotensin II and thereby potentiate synovial hypoxia and proliferation in rheumatoid arthritis.

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  1. Kenny AJ, Stephenson SL, Turner AJ. Cell surface peptidases. In: Kenny AJ, Turner AJ, eds. Mammalian ectoenzymes. Oxford: Elsevier, 1987:169-210.
  2. Walsh, Catravas, Wharton on July 29, 2023 by guest. Protected by copyright. http://ard.bmj.com/ Ann Rheum Dis: first published as 10.1136/ard.59.2.125 on 1 February 2000. Downloaded from

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Authors
Walsh, D. A., Catravas, J., & Wharton, J.
Affiliations
University of Nottingham (GB)
Corresponding author
Walsh, David Andrew
Venue
Annals of the Rheumatic Diseases
Publisher
Elsevier BV
Published
2000-02
Volume
59
Issue
2
Pages
125-131
ISSN
0003-4967 (ISSN-L)
OpenAlex
W2101924426
Cited by
57
References
45
Citations by year
2026: 1 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 5 · 2016: 5 · 2015: 7 · 2014: 3 · 2013: 3
FWCI
0.23
Type
journal article
Language
en
Open access
Locations
  • Annals of the Rheumatic Diseases (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
Keywords
angiotensin-converting enzyme, synovium, rheumatoid arthritis, osteoarthritis, chondromalacia patellae, angiotensin II, synovitis, microvascular endothelium, enzyme up-regulation, cell proliferation
MeSH terms
Adult, Aged, Angiotensin-Converting Enzyme Inhibitors, Arthritis, Rheumatoid, Cartilage Diseases, Dipeptides, Female, Humans, Immunoenzyme Techniques, Iodine Radioisotopes, Peptidyl-Dipeptidase A, Male, Middle Aged, Osteoarthritis, Synovial Membrane, Stromal Cells

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