Skip to content

Research at St Andrews

A therapeutic antibody targeting osteoprotegerin attenuates severe experimental pulmonary arterial hypertension

Research output: Contribution to journalArticlepeer-review

Author(s)

Nadine D Arnold, Josephine A Pickworth, Laura E West, Sarah Dawson, Joana A Carvalho, Helen Casbolt, Adam T Braithwaite, James Iremonger, Lewis Renshall, Volker Germaschewski, Matthew McCourt, Philip Bland-Ward, Hager Kowash, Abdul G Hameed, Alexander M K Rothman, Maria G Frid, A A Roger Thompson, Holly R Evans, Mark Southwood, Nicholas W Morrell & 7 more David C Crossman, Moira K B Whyte, Kurt R Stenmark, Christopher M Newman, David G Kiely, Sheila E Francis, Allan Lawrie

School/Research organisations

Abstract

Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Current treatments increase life expectancy but have limited impact on the progressive pulmonary vascular remodelling that drives PAH. Osteoprotegerin (OPG) is increased within serum and lesions of patients with idiopathic PAH and is a mitogen and migratory stimulus for pulmonary artery smooth muscle cells (PASMCs). Here, we report that the pro-proliferative and migratory phenotype in PASMCs stimulated with OPG is mediated via the Fas receptor and that treatment with a human antibody targeting OPG can attenuate pulmonary vascular remodelling associated with PAH in multiple rodent models of early and late treatment. We also demonstrate that the therapeutic efficacy of the anti-OPG antibody approach in the presence of standard of care vasodilator therapy is mediated by a reduction in pulmonary vascular remodelling. Targeting OPG with a therapeutic antibody is a potential treatment strategy in PAH.

Close

Details

Original languageEnglish
Article number5183
Number of pages18
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 15 Nov 2019

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial

    Mullen, M., Jin, X. Y., Child, A., Stuart, A. G., Dodd, M., Aragon-Martin, J. A., Gaze, D., Kiotsekoglou, A., Yuan, L., Hu, J., Foley, C., Van Dyck, L., Knight, R., Clayton, T., Swan, L., Thomson, J. D. R., Erdem, G., Crossman, D., Flather, M. & AIMS Investigators, 21 Dec 2019, In: Lancet. 394, 10216, p. 2263-2270

    Research output: Contribution to journalArticlepeer-review

  2. Interleukin-1 beta inhibition with canakinumab and reducing lung cancer-subset analysis of the canakinumab anti-inflammatory thrombosis outcome study trial (CANTOS)

    Crossman, D. & Rothman, A. M. K., 18 Sep 2018, In: Journal of Thoracic Disease. 10, Suppl 26, p. S3084-S3087

    Research output: Contribution to journalEditorialpeer-review

  3. Dietary docosahexaenoic acid reduces oscillatory wall shear stress, atherosclerosis and hypertension, most likely mediated via an IL-1-mediated mechanism

    Alfaida, M., Chamberlain, J., Rothman, A., Crossman, D. C., Villa-Uriol, M-C., Hadoke, P., Wu, J., Schenkel, T., Evans, P. & Francis, S., 3 Jul 2018, In: Journal of the American Heart Association. 7, 13, 19 p., e008757.

    Research output: Contribution to journalArticlepeer-review

  4. ATP evokes Ca2+ responses and CXCL5 secretion via P2X4 receptor activation in human monocyte-derived macrophages

    Layhadi, J. A., Turner, J., Crossman, D. & Fountain, S. J., 1 Feb 2018, In: The Journal of Immunology. 200, 3, p. 1159-1168

    Research output: Contribution to journalArticlepeer-review

  5. Canakinumab for atherosclerotic disease

    MRC-ILA Heart investigators, Rothman, A. M., Morton, A. C. & Crossman, D. C., 11 Jan 2018, In: New England Journal of Medicine. 378, 2, p. 197-8 2 p.

    Research output: Contribution to journalArticlepeer-review

Related by journal

  1. Nature Communications (Journal)

    Ife Okafor-Yarwood (Reviewer)

    23 Mar 2020

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

  2. Nature Communications (Journal)

    Andy Gardner (Reviewer)

    Feb 2018

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

Related by journal

  1. A rotary mechanism for allostery in bacterial hybrid malic enzymes

    Harding, C. J., Cadby, I. T., Moynihan, P. J. & Lovering, A. L., 23 Feb 2021, In: Nature Communications. 12, 12 p., 1228.

    Research output: Contribution to journalArticlepeer-review

  2. DNA methylation predicts age and provides insight into exceptional longevity of bats

    Wilkinson, G. S., Adams, D. M., Haghani, A., Lu, A. T., Zoller, J., Breeze, C. E., Arnold, B. D., Ball, H. C., Carter, G. G., Cooper, L. N., Dechmann, D. K. N., Devanna, P., Fasel, N. J., Galazyuk, A. V., Günther, L., Hurme, E., Jones, G., Knörnschild, M., Lattenkamp, E. Z., Li, C. Z. & 14 others, Mayer, F., Reinhardt, J. A., Medellin, R. A., Nagy, M., Pope, B., Power, M. L., Ransome, R. D., Teeling, E. C., Vernes, S. C., Zamora-Mejías, D., Zhang, J., Faure, P. A., Greville, L. J. & Horvath, S., 12 Mar 2021, In: Nature Communications. 12, 13 p., 1615.

    Research output: Contribution to journalArticlepeer-review

  3. Rapid parallel adaptation despite gene flow in silent crickets

    Zhang, X., Rayner, J. G., Blaxter, M. & Bailey, N. W., 4 Jan 2021, In: Nature Communications. 12, 15 p., 50.

    Research output: Contribution to journalArticlepeer-review

  4. Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

    Demontis, D., Walters, R. K., Rajagopal, V. M., Waldman, I. D., Grove, J., Als, T. D., Dalsgaard, S., Ribasas, M., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Werge, T., Nordentoft, M., Mors, O., Mortensen, P. B., (PGC), ADHD. W. G. O. T. P. G. C., Andreassen, O. A., Arranz, M. J., Banaschewski, T., Bau, C., Bellgrove, M. & 56 others, Biederman, J., Brikell, I., Buitelaar, J. K., Burton, C. L., Casas, M., Crosbie, J., Doyle, A. E., Ebstein, R. P., Elia, J., Elizabeth, C. C., Grevet, E., Grizenko, N., Havdahl, A., Hawi, Z., Hebebrand, J., Hervas, A., Hohmann, S., Haavik, J., Joober, R., Kent, L., Kuntsi, J., Langley, K., Larsson, H., Lesch, K-P., Leung, P. W. L., Liao, C., Loo, S. K., Martin, J., Martin, N. G., Medland, S. E., Miranda, A., Mota, N. R., Oades, R. D., Ramos-Quiroga, J. A., Reif, A., Rietschel, M., Roeyers, H., Rohde, L. A., Rothenberger, A., Rovira, P., Sánchez-Mora, C., Schachar, R. J., Sengupta, S., Artigas, M. S., Steinhausen, H-C., Thapar, A., Witt, S. H., Yang, L., Zayats, T., Zhang-James, Y., Cormand, B., Hougaard, D. M., Neale, B. M., Franke, B., Faraone, S. V. & Børglum, A. D., 25 Jan 2021, In: Nature Communications. 12, 1, 12 p., 576 .

    Research output: Contribution to journalArticlepeer-review

  5. "Gene accordions" cause genotypic and phenotypic heterogeneity in clonal populations of Staphylococcus aureus

    Belikova, D., Jochim, A., Power, J., Holden, M. T. G. & Heilbronner, S., 14 Jul 2020, In: Nature Communications. 11, 15 p., 3526.

    Research output: Contribution to journalArticlepeer-review

ID: 263392099

Top