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    Neoangiogenesis and rheumatoid arthritis

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    Principal investigator:  Jérôme Avouac

    Contact : jerome.avouac@inserm.fr  Phone: +33 1 40 51 65 17

     

    Objectives

    Rheumatoid arthritis (RA) is the most frequent inflammatory rheumatic disorder. It is a chronic autoimmune disease characterized by a chronic inflammation of the synovial tissue causing cartilage destruction, bone erosion, pain, and disability. Current RA therapies target the inflammatory consequences of autoimmune activation with the use of synthetic and biologic disease-modifying antirheumatic drugs. Despite the efficacy of agents, 30% of patients seem to have no response or no sustained response. This primary or secondary lack of clinical response upon treatments targeting inflammation supports the need to develop new complementary therapeutic strategies.

    The synovium is the primary site of the inflammatory process, which if untreated leads to irreversible damage to the adjacent cartilage and bone. Formation of new blood vessels is an early and crucial event to promote the development of the hyperplasic proliferative pathologic synovium. Endothelial cells are critical for the formation of new blood vessels since they highly contribute to angiogenesis and vasculogenesis.

    Our objective is to identify new actors of synovial angiogenesis through unbiased strategies performed on endothelial cells derived from circulating progenitors issued from patients with RA. The expression of identified candidates is then assessed in endothelial cells, synovial cells, synovial fluid, serum and synovial tissue. The expression or activity of identified candidates is then modulated by complementary approaches to study the functional properties of endothelial cells. The effects of the modulation of target expression or activity are then studied in vivo in mouse models of neoangiogenesis and experimental arthritis.

    Our ambition is to identify new relevant biomarkers of disease activity or severity in order to improve patient stratification and develop new therapeutic strategies based on synovial angiogenesis targeting, which could be used as an adjuvant treatment of RA, synergistic with the inhibition of immune-mediated inflammation.

    We are developing in parallel clinical and epidemiological research aiming at the development of a personalized medicine approach in RA, which consists on adapting the right treatment at the right time to the right patient, in order to enhance therapeutic chances, facilitate decision-making and reduce healthcare costs.

     

    People

    Yannick Allanore, PU-PH, MD, PhD, Lab director

    Jérome Avouac, MCU-PH, MD, PhD, Associate professor

    Sonia Pezet, technician

    Agathe Leblond, PhD student

     

    Funding

    • INSERM : ATIP/AVENIR Programme
    • Société Française de Rhumatologie
    • Fondation Arthritis
    • Bourse passerelle Pfizer
    • Appel d’offre interne Groupe Hospitaliser Cochin Paris Centre

     

    Main publications

    Leblond A, Allanore Y, Avouac J. Targeting synovial neoangiogenesis in rheumatoid arthritis. Autoimmun Rev. 2017 Jun;16(6):594-601.

    Avouac J, Amrouche F, Meune C, Rey G, Kahan A, Allanore Y. Mortality profile of patients with rheumatoid arthritis in France and its change in 10 years. Semin Arthritis Rheum. 2017 Apr;46(5):537-543.

    Poiroux L, Allanore Y, Kahan A, Avouac J. All-cause Mortality Associated with TNF-α Inhibitors in Rheumatoid Arthritis: A Meta-Analysis of Randomized Controlled Trials. Am J Med. 2015 Dec;128(12):1367-73.

    Elhai M, Chiocchia G, Marchiol C, Lager F, Renault G, Colonna M, Bernhardt G, Allanore Y, Avouac J. Targeting CD226/DNAX accessory molecule-1 (DNAM-1) in collagen-induced arthritis mouse models. J Inflamm (Lond). 2015 Feb 8;12:9.

    Avouac J, Meune C, Chenevier-Gobeaux C, Dieudé P, Borderie D, Lefevre G, Kahan A, Allanore Y. Inflammation and disease activity are associated with high circulating cardiac markers in rheumatoid arthritis independently of traditional cardiovascular risk factors. J Rheumatol. 2014 Feb;41(2):248-55.

    Jodon de Villeroché V, Avouac J, Ponceau A, Ruiz B, Kahan A, Boileau C, Uzan G, Allanore Y. Enhanced late-outgrowth circulating endothelial progenitor cell levels in rheumatoid arthritis and correlation with disease activity. Arthritis Res Ther. 2010;12(1):R27.

    Avouac J, Allanore Y. Cardiovascular risk in rheumatoid arthritis: effects of anti-TNF drugs. Expert Opin Pharmacother. 2008 May;9(7):1121-8.

    Avouac J, Uzan G, Kahan A, Boileau C, Allanore Y. Endothelial progenitor cells and rheumatic disorders. Joint Bone Spine. 2008 Mar;75(2):131-7.

     

     

     

     

     

     

     

     

     

     

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