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

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.

• Authors: D A Walsh, J Catravas, J Wharton
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 59 Issue 2 Pg. 125-31 (Feb 2000) ISSN: 0003-4967 [Print] England
• PMID: 10666168 (Publication Type: Journal Article)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Dipeptides
• Iodine Radioisotopes
• L-proline, N2-((1S)-1-carboxy-3-phenylpropyl)-N6-((4-hydroxyphenyl)iminomethyl)-L-lysyl-
• Peptidyl-Dipeptidase A

Topics

• Adult
• Aged
• Angiotensin-Converting Enzyme Inhibitors (metabolism)
• Arthritis, Rheumatoid (enzymology)
• Cartilage Diseases (enzymology)
• Dipeptides (metabolism)
• Female
• Humans
• Immunoenzyme Techniques
• Iodine Radioisotopes
• Male
• Middle Aged
• Osteoarthritis (enzymology)
• Peptidyl-Dipeptidase A (metabolism)
• Stromal Cells (enzymology)
• Synovial Membrane (enzymology)