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Idiopathic and Familial Pulmonary Arterial Hypertension

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Molecular Basis of Pulmonary Disease

Part of the book series: Respiratory Medicine ((RM))

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Abstract

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease that is defined hemodynamically. The average life expectancy after diagnosis is short, with death usually due to progressive right ventricular hypertrophy and right heart failure. PAH results from vasoconstriction and structural alterations to the pulmonary vasculature. PAH can be secondary to other disorders, including underlying lung disease or it can be idiopathic without a known predisposing condition. Primary or idiopathic PAH is rare and includes individuals with a family history of disease. This chapter will focus on idiopathic and familial PAH. The discovery and history of the disease, incidence, development of the clinical classification, epidemiology, prognostic factors, and clinical assessment are reviewed. The pathology of vascular remodeling is described, including the potential sequence of events, cell types, and processes involved. The genetics of the disease together with the identification of frequent mutations in the BMPR2 gene in familial and idiopathic patients is presented. Stresses or pathways that may play a role in triggering PAH in patients with BMPR2 mutations is reviewed because of the low penetrance of symptomatic disease in families with BMPR2 mutations. Potential stimuli and pathways that can trigger the disease have been identified from clinical studies of PAH patients and from experimental models of PAH. Current therapies for PAH including general management, pharmacologic, and surgical are reviewed. Future directions in diagnosis, management, pharmacotherapies, genetic studies, pathobiology, and potential cell-based therapies are also discussed.

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Acknowledgments

This work was supported by NIH awards HL72894 (TDLC), HL061997 (WCN), HL072058 (WCN), and an American Heart Association Established Investigator Award 0740069 N (TDLC).

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Authors and Affiliations

  1. Department of Internal Medicine, University of Cincinnati School of Medicine, Cincinnati, OH, USA

    Jean M. Elwing MD

  2. Department of Pathology, Seattle Children’s Hospital, Seattle, WA, USA

    Gail H. Deutsch MD

  3. Department of Pediatrics, University of Cincinnati School of Medicine and Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    William C. Nichols PhD & Timothy D. Le Cras PhD

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  1. Jean M. Elwing MD
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  2. Gail H. Deutsch MD
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Editors and Affiliations

  1. Div. Pulmonary & Critical Care, University of Cincinnati, Albert Sabin Way 231, Cincinnati, 45267, USA

    Francis X. McCormack

  2. Div. Pulmonary & Critical Care, University of Cincinnati, Albert Sabin Way 231, Cincinnati, 45267, USA

    Ralph J. Panos

  3. Medical Center, Cincinnati Children's Hospital, Burnet Ave. 3333, Cincinnati, 45229, USA

    Bruce C. Trapnell

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Elwing, J.M., Deutsch, G.H., Nichols, W.C., Le Cras, T.D. (2010). Idiopathic and Familial Pulmonary Arterial Hypertension. In: McCormack, F., Panos, R., Trapnell, B. (eds) Molecular Basis of Pulmonary Disease. Respiratory Medicine. Humana Press. https://doi.org/10.1007/978-1-59745-384-4_3

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