ISSN 1016-5169 | E-ISSN 1308-4488
Archives of the Turkish Society of Cardiology
Relevant issues in the pathology and pathobiology of pulmonary hypertension [Turk Kardiyol Dern Ars]
Turk Kardiyol Dern Ars. 2014; 42(1): 5-16

Relevant issues in the pathology and pathobiology of pulmonary hypertension

Rubin M. Tuder1, Stephen L. Archer2, Peter Dorfmüller3, Serpil C. Erzurum4, Christophe Guignabert5, Evangelos Michelakis6, Marlene Rabinovitch7, Ralph Schermuly8, Kurt R. Stenmark9, Nicholas W. Morrell10
1University of Colorado School of Medicine, Department of Medicine, Translational Lung Research Program, Aurora, Colorado, USA
2Queen's University, Department of Medicine, Kingston, Ontario, Canada
3Paris-Sud University, Maria Lannelongu Hospital, Department of Pathology, Le Plessis-Robinson, France
4Lerner Research Institute and Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA
5INSERM UMR 999, LABEX Lermit, Paris-Sud Medical School and Maria Lannelongu Hospital, Kremlin-Bicêtre, France
6Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada
7Stanford University School of Medicine, Cardiovascular Institute and Department of Pediatrics, Vera Moulton Wall Center for Pulmonary Vascular Disease at Stanford, California, USA
8University of Giessen and Marburg Lung Center, Cardiopulmonary System (Excellence Cluster) German Lung Center, Giessen, Germany
9University of Colorado School of Medicine, Department of Pediatrics, Cardiovascular Pulmonary Laboratory, Aurora, Colorado, USA
10Cambridge University, Faculty of Medicine, Department of Medicine, Cambridge, England

Knowledge of the pathobiology of pulmonary hypertension (PH) continues to accelerate. However, fundamental gaps remain in our understanding of the underlying pathological changes in pulmonary arteries and veins in the different forms of this syndrome. Although PH primarily affects the arteries, venous disease is increasingly recognized as an important entity. Moreover, prognosis in PH is determined largely by the status of the right ventricle, rather than the levels of pulmonary artery pressures. It is increasingly clear that although vasospasm plays a role, PH is an obstructive lung panvasculopathy. Disordered metabolism and mitochondrial structure, inflammation, and dysregulation of growth factors lead to a proliferative, apoptosis-resistant state. These abnormalities may be acquired, genetically mediated as a result of mutations in bone morphogenetic protein receptor-2 or activin-like kinase-1, or epigenetically inherited (as a result of epigenetic silencing of genes such as superoxide dismutase-2). There is a pressing need to better understand how the pathobiology leads to severe disease in some patients versus mild PH in others. Recent recognition of a potential role of acquired abnormalities of mitochondrial metabolism in the right ventricular myocytes and pulmonary vascular cells suggests new therapeutic approaches, diagnostic modalities, and biomarkers. Finally, dissection of the role of pulmonary inflammation in the initiation and promotion of PH has revealed a complex yet fascinating interplay with pulmonary vascular remodeling, promising to lead to novel therapeutics and diagnostics. Emerging concepts are also relevant to the pathobiology of PH, including a role for bone marrow and circulating progenitor cells and microribonucleic acids. Continued interest in the interface of the genetic basis of PH and cellular and molecular pathogenetic links should further expand our understanding of the disease. (J Am Coll Cardiol 2013;62: D4–12) ª 2013 by the American College of Cardiology Foundation.

Keywords: Inflammation, metabolism, pulmonary arteries, pulmonary veins

How to cite this article
Rubin M. Tuder, Stephen L. Archer, Peter Dorfmüller, Serpil C. Erzurum, Christophe Guignabert, Evangelos Michelakis, Marlene Rabinovitch, Ralph Schermuly, Kurt R. Stenmark, Nicholas W. Morrell. Relevant issues in the pathology and pathobiology of pulmonary hypertension. Turk Kardiyol Dern Ars. 2014; 42(1): 5-16

Corresponding Author: Rubin M. Tuder, United States
Manuscript Language: Turkish


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