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Pathogenesis of Pulmonary Arterial Hypertension

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Scleroderma

Abstract

The development of pulmonary arterial hypertension (PAH) represents a serious comorbidity in collagen vascular diseases. This complication is commonly observed in scleroderma (SSc) patients where the risk of developing PAH persists throughout the disease. Affecting up to 10 % of patients, SSc appears to act as a susceptibility factor in the development of PAH (Avouac J, Airo P, Meune C, Beretta L, Dieude P, Caramaschi P, et al. Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians and metaanalysis of 5 studies. J Rheumatol. 2010;37(11):2290–8. Nihtyanova SI, Schreiber BE, Ong VH, Rosenberg D, Moinzadeh P, Coghlan JG, et al. Prediction of pulmonary complications and long-term survival in systemic sclerosis. Arthritis Rheum. 2014;66(6):1625–35). While significant progress has been made in understanding the pathological mechanisms that contribute to the development and progression of heritable and idiopathic forms of PAH, the relative pathogenic mechanisms that contribute to the development of PAH in SSc patients remain less appreciated. Indeed SSc-PAH patients have a significantly poorer prognosis compared to other forms (Mathai SC, Hummers LK, Champion HC, Wigley FM, Zaiman A, Hassoun PM, et al. Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease. Arthritis Rheum. 2009;60(2):569–77). Here we discuss the key pathological findings in PAH and fundamental pathobiological mechanisms implicated in the development and progression of PAH, particularly in SSc patients.

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Acknowledgments

RMT was supported by; AH was supported by the Arthritis Research UK.

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Authors and Affiliations

  1. Division of Pulmonary Science & Critical Care Medicine, Department of Medicine, University of Colorado Denver, Aurora, CO, USA

    Rubin M. Tuder MD

  2. Centre for Rheumatology and Connective Tissue Disease, Royal Free Hospital (University College London), London, UK

    Markella Ponticos PhD

  3. Drug Discovery Group, Translational Research Office, School of Pharmacy, University College London, London, UK

    Alan Holmes PhD

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  1. Rubin M. Tuder MD
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  2. Markella Ponticos PhD
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  3. Alan Holmes PhD
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Correspondence to Rubin M. Tuder MD .

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Editors and Affiliations

  1. Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

    John Varga

  2. Division of Medicine, Department of Inflammation, Centre for Rheumatology and Connective Tissue Diseases, UCL Division of Medicine, Royal Free Hospital, London, United Kingdom

    Christopher P. Denton

  3. Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA

    Fredrick M. Wigley

  4. Service de Rhumatologie A, INSERMU1016, Universit. Paris Descartes, Hôpital Cochin, Paris, France

    Yannick Allanore

  5. Department of Allergy and Rheumatology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan

    Masataka Kuwana

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Tuder, R.M., Ponticos, M., Holmes, A. (2017). Pathogenesis of Pulmonary Arterial Hypertension. In: Varga, J., Denton, C., Wigley, F., Allanore, Y., Kuwana, M. (eds) Scleroderma. Springer, Cham. https://doi.org/10.1007/978-3-319-31407-5_26

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