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

doi:10.1136/ard.59.2.125

Annals of the Rheumatic Diseases 2000;59:125-131; doi:10.1136/ard.59.2.125

Ann Rheum Dis 2000;59:125-131 ( February )

Extended report

Angiotensin converting enzyme in human synovium: increased stromal [¹²⁵I]351A binding in rheumatoid arthritis David Andrew Walsh^a, John Catravas^b, John Wharton^c

^a Academic Rheumatology, University of Nottingham Clinical Sciences Building, City Hospital, Nottingham NG5 1PB , ^b Vascular Biology Center, Medical College of Georgia, Augusta, Georgia USA, ^c Department of Histochemistry, Imperial College School of Medicine, Hammersmith Campus, London

Correspondence to: Dr Walsh

Accepted for publication 22 October 1999

OBJECTIVE $---$ To determine whether tissue angiotensin converting enzyme (ACE) is increased in synovia from patients with rheumatoid arthritis,osteoarthritis or chondromalaciapatellae.
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 bindingof the ACE inhibitor [¹²⁵I]351A. The amount of ACE was measured with computer assistedimage analysis as the proportion of synovial section area occupiedby ACE-immunoreactive cells, and the density of [¹²⁵I]351Abinding.
RESULTS $---$ [¹²⁵I]351A binding sites had characteristics of ACE and colocalised with ACE-like immunoreactivity to microvascular endotheliumand fibroblast-like stromal cells in inflamed and non-inflamedhuman synovium. Stromal [¹²⁵I]351A binding densities (B_eq) and the fraction of synovial sectionarea occupied by ACE-immunoreactivity (fractional area) were higherin synovia from patients with rheumatoid arthritis (B_eq 28 amol/mm², fractional area 0.21) than from those with osteoarthritis (B_eq9 amol/mm², fractional area 0.10) or chondromalacia patellae (B_eq 9 amol/mm², fractional area 0.09)(p < 0.05). Density of [¹²⁵I]351A binding to stroma was similar to that to blood vesselsin rheumatoid arthritis, but less dense than vascular bindingin chondromalacia patellae and osteoarthritis. Increases in [¹²⁵I]351A binding densities were attributable to increases in thenumbers of binding sites, and were consistent with an increasein the density of ACE bearing stromalcells.
CONCLUSION $---$ ACE is upregulated in synovial stroma in rheumatoid arthritis. Increased tissue ACE may result in increased local generationof the vasoconstrictor and mitogenic peptide angiotensin II andthereby potentiate synovial hypoxia and proliferation in rheumatoidarthritis.

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