Angiotensin converting enzyme in human synovium: increased stromal [125I]351A binding in rheumatoid arthritis
Open accessAbstract
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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ACE is upregulated in synovial tissue of patients with rheumatoid arthritis, leading to higher availability of angiotensin II in inflamed joints.
“ACE is upregulated in synovial tissue of patients with RA, leading to higher availability of angiotensin II in inflamed joints [144].”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [144]
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Cites
Arnett, F. C., Edworthy, S. M., Bloch, D. A., McShane, D. J., Fries, J. F., Cooper, N. S., Healey, L. A., Kaplan, S. R., Liang, M. H., Luthra, H. S., et al. (1988) · Arthritis & Rheumatism · doi:10.1002/art.1780310302 · Cited by 19,753 · see citing works
Hsu, S. M., Raine, L., & Fanger, H. (1981) · Journal of Histochemistry & Cytochemistry · doi:10.1177/29.4.6166661 · Cited by 14,248 · see citing works
Angiogenesis in cancer, vascular, rheumatoid and other disease
Folkman, J. (1995) · Nature Medicine · doi:10.1038/nm0195-27 · Cited by 7,627 · see citing works
Altman, R., Asch, E., Bloch, D., Bole, G., Borenstein, D., Brandt, K., Christy, W., Cooke, T. D., Greenwald, R., Hochberg, M., et al. (1986) · Arthritis & Rheumatism · doi:10.1002/art.1780290816 · Cited by 6,777 · see citing works
Angiotensin II receptors and angiotensin II receptor antagonists.
Timmermans, P. B. M. W. M., Wong, P. C., Chiu, A. T., Herblin, W. F., Benfield, P. A., Carini, D. J., Lee, R. J., Wexler, R. R., Saye, J. A., & Smith, R. D. (1993) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)00446-6 · Cited by 1,854 · see citing works
Sadoshima, J., & Izumo, S. (1993) · Circulation Research · doi:10.1161/01.res.73.3.413 · Cited by 1,427 · see citing works
The glucose oxidase-DAB-nickel method in peroxidase histochemistry of the nervous system
Shu, S., Ju, G., & Fan, L. (1988) · Neuroscience Letters · doi:10.1016/0304-3940(88)90346-1 · Cited by 1,235 · see citing works
Brilla, C. G., Zhou, G., Matsubara, L. S., & Weber, K. T. (1994) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1994.1098 · Cited by 693 · see citing works
Stimulation of connective tissue cell growth by substance P and substance K
Nilsson, J., von Euler, A. M., & Dalsgaard, C.-J. (1985) · Nature · doi:10.1038/315061a0 · Cited by 679 · see citing works
Captopril inhibits angiogenesis and slows the growth of experimental tumors in rats.
Volpert, O. V., Ward, W. F., Lingen, M. W., Chesler, L., Solt, D. B., Johnson, M. D., Molteni, A., Polverini, P. J., & Bouck, N. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118838 · Cited by 323 · see citing works
Neuropeptide degrading enzymes in normal and inflamed human synovium.
Walsh, D. A., Mapp, P. I., Wharton, J., et al. (1993) · PubMed · Cited by 218 · see citing works
Self-citationCardiac angiotensin converting enzyme and myocardial fibrosis in the rat
Sun, Y., Cleutjens, J. P. M., Diaz‐Arias, A. A., et al. (1994) · Cardiovascular Research · doi:10.1093/cvr/28.9.1423 · Cited by 198 · see citing works
Smits, J. F. M., van Krimpen, C., Schoemaker, R. G., et al. (1992) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199211000-00013 · Cited by 183 · see citing works
CAPTOPRIL: A NEW TREATMENT FOR RHEUMATOID ARTHRITIS?
MARTIN, M. F. R., Mckenna, F., Bird, H. A., Surrall, K. E., Dixon, J. S., & Wright, V. A. (1984) · The Lancet · doi:10.1016/s0140-6736(84)91821-x · Cited by 159 · see citing works
VANKRIMPEN, C., Smits, J. F. M., Cleutjens, J. P. M., et al. (1991) · Journal of Molecular and Cellular Cardiology · doi:10.1016/0022-2828(91)90082-w · Cited by 155 · see citing works
Fan, T. D., Hu, D., Guard, S. E., et al. (1993) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1993.tb13769.x · Cited by 135 · see citing works
Focally regulated endothelial proliferation and cell death in human synovium.
Walsh, D. A., Wade, M., Mapp, P. I., & Blake, D. R. (1998) · Europe PMC (PubMed Central) · Cited by 118 · see citing works
Self-citationCultured Myofibroblasts Generate Angiotensin Peptidesde Novo
Katwa, L. C., Campbell, S. E., Tyagi, S. C., Lee, S. J., Cicila, G. T., & Weber, K. T. (1997) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1997.0376 · Cited by 116 · see citing works
Fisher, S. A., & Absher, M. P. (1995) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1995.268.4.c910 · Cited by 96 · see citing works
Inhibitor binding assay for angiotensin-converting enzyme.
Fyhrquist, F., Tikkanen, I., Grönhagen-Riska, C., et al. (1984) · Clinical Chemistry · doi:10.1093/clinchem/30.5.696 · Cited by 70 · see citing works
Walsh, D. A., Hu, D., Wharton, J., Catravas, J. D., Blake, D. R., & Fan, T. D. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701062 · Cited by 69 · see citing works
Self-citationUnger, T., & Gohlke, P. (1990) · The American Journal of Cardiology · doi:10.1016/0002-9149(90)90118-k · Cited by 67 · see citing works
Bathon, J. M., Manning, D. C., GOLDMAN, D. W., Towns, M. C., & Proud, D. (1992) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)11244-5 · Cited by 66 · see citing works
Angiotensin-converting enzyme and wound healing in diverse tissues of the rat
Sun, Y., & Weber, K. T. (1996) · Journal of Laboratory and Clinical Medicine · doi:10.1016/s0022-2143(96)90170-5 · Cited by 63 · see citing works
Hafizi, S., Wharton, J., Morgan, K., et al. (1998) · Circulation · doi:10.1161/01.cir.98.23.2553 · Cited by 60 · see citing works
Self-citationMacrophage and myofibroblast proliferation in remnant kidney: role of angiotensin II.
Wu, L. L., Yang, N., Roe, C. J., et al. (1997) · PubMed · Cited by 57 · see citing works
AT1 receptor characteristics of angiotensin analogue binding in human synovium
Walsh, D. A., Suzuki, T., Knock, G. A., Blake, D. R., Polak, J. M., & Wharton, J. (1994) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1994.tb13091.x · Cited by 52 · see citing works
Self-citationMendelsohn, F. A. O. (1984) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.1984.tb00294.x · Cited by 51 · see citing works
Metsarinne, K. P., Nordström, D., Konttinen, Y. T., et al. (1992) · Rheumatology International · doi:10.1007/bf00290261 · Cited by 49 · see citing works
Production of angiotensin converting enzyme by rheumatoid synovial membrane.
Veale, D. J., Yanni, G., Bresnihan, B., & FitzGerald, O. (1992) · Annals of the Rheumatic Diseases · doi:10.1136/ard.51.4.476 · Cited by 45 · see citing works
Angiotensin I-converting enzyme localization on cultured fibroblasts by immunofluorescence
Weinberg, K. S., DOUGLAS, W. H. J., MacNamee, D. R., et al. (1982) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02796341 · Cited by 44 · see citing works
Challah, M., Nicoletti, A., Arnal, J., et al. (1995) · Cardiovascular Research · doi:10.1016/s0008-6363(96)88516-6 · Cited by 36 · see citing works
Bird, H. A., Gallez, P. L., Dixon, J. S., et al. (1990) · PubMed · Cited by 34 · see citing works
Microvascular substance P binding to normal and inflamed rat and human synovium.
Walsh, D. A., Salmon, M., Mapp, P. I., et al. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)39371-7 · Cited by 32 · see citing works
Self-citationCaspritz, G., Alpermann, H. G., & Schleyerbach, R. (1986) · PubMed · Cited by 24 · see citing works
Mosaic expression of membrane peptidases by confluent cultures of Caco‐2 cells
Howell, S. A., Brewis, I. A., Hooper, N. M., et al. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)81502-q · Cited by 22 · see citing works
Serum and synovial fluid levels of angiotensin converting enzyme in polyarthritis.
Lowe, J. R., Dixon, J. S., Guthrie, J. A., & McWhinney, P. H. M. (1986) · Annals of the Rheumatic Diseases · doi:10.1136/ard.45.11.921 · Cited by 21 · see citing works
Subissi, A., Guelfi, M., & Criscuoli, M. (1990) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1990.tb15837.x · Cited by 20 · see citing works
Prorenin-Renin Axis in Synovial Fluid in Patients with Rheumatoid Arthritis and Osteoarthritis.
Izai, M., MIYAZAKI, S., MURAI, R., et al. (1992) · Endocrinologia Japonica · doi:10.1507/endocrj1954.39.259 · Cited by 15 · see citing works
Angiotensin-Converting Enzyme Substrates Hydrolyzed by Fibroblasts and Vascular Endothelial Cells
Rubin, D. B., Mason, R. J., & Dobbs, L. G. (1982) · Experimental Lung Research · doi:10.3109/01902148209063288 · Cited by 14 · see citing works
Walsh, D. A., & Fan, T. D. (1997) · Elsevier eBooks · doi:10.1016/b978-012249340-9/50020-6 · Cited by 13 · see citing works
Self-citationChallah, M. (1995) · Cardiovascular Research · doi:10.1016/0008-6363(96)88516-6 · Cited by 13 · see citing works
Corrêa, F. M. D. A., Guilhaume, S. S., & Saavedra, J. M. (1991) · Brain Research · doi:10.1016/0006-8993(91)91289-d · Cited by 12 · see citing works
Differential distribution of angiotensin AT2 receptors in the normal and failing human heart.
Wharton, J., Morgan, K., Rutherford, R. A. D., Catravas, J., Chester, A., Whitehead, B. F., de Leval, M., Yacoub, M., & Polak, J. M. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37201-5 · Cited by 11 · see citing works
Self-citationCatt, K. J., & Baukal, A. J. (1973) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(73)90203-1 · Cited by 7 · see citing works
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Research works printed but not linked: 2
- Kenny AJ, Stephenson SL, Turner AJ. Cell surface peptidases. In: Kenny AJ, Turner AJ, eds. Mammalian ectoenzymes. Oxford: Elsevier, 1987:169-210.
- 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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Interaction of the endocrine system with inflammation: a function of energy and volume regulation
Straub, R. H. (2014) · Arthritis Research & Therapy · doi:10.1186/ar4484 · Cited by 121 · see citing works
“ACE is upregulated in synovial tissue of patients with RA, leading to higher availability of angiotensin II in inflamed joints [144].”
BackgroundSagawa, K., Nagatani, K., Komagata, Y., & Yamamoto, K. (2005) · Arthritis & Rheumatism · doi:10.1002/art.21040 · Cited by 83 · see citing works
The non-thiol angiotensin-converting enzyme inhibitor quinapril suppresses inflammatory arthritis
Dalbeth, N. (2005) · Rheumatology · doi:10.1093/rheumatology/keh398 · Cited by 61 · see citing works
- 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
- bronze
- doi.org
- 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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