title: Inflammation, growth factors, and pulmonary vascular remodeling.
abstract: Inflammatory processes are prominent in various types of human and experimental pulmonary hypertension (PH) and are increasingly recognized as major pathogenic components of pulmonary vascular remodeling. Macrophages, T and B lymphocytes, and dendritic cells are present in the vascular lesions of PH, whether in idiopathic pulmonary arterial hypertension (PAH) or PAH related to more classical forms of inflammatory syndromes such as connective tissue diseases, human immunodeficiency virus (HIV), or other viral etiologies. Similarly, the presence of circulating chemokines and cytokines, viral protein components (e.g., HIV-1 Nef), and increased expression of growth (such as vascular endothelial growth factor and platelet-derived growth factor) and transcriptional (e.g., nuclear factor of activated T cells or NFAT) factors in these patients are thought to contribute directly to further recruitment of inflammatory cells and proliferation of smooth muscle and endothelial cells. Other processes, such as mitochondrial and ion channel dysregulation, seem to convey a state of cellular resistance to apoptosis; this has recently emerged as a necessary event in the pathogenesis of pulmonary vascular remodeling. Thus, the recognition of complex inflammatory disturbances in the vascular remodeling process offers potential specific targets for therapy and has recently led to clinical trials investigating, for example, the use of tyrosine kinase inhibitors. This paper provides an overview of specific inflammatory pathways involving cells, chemokines and cytokines, cellular dysfunctions, growth factors, and viral proteins, highlighting their potential role in pulmonary vascular remodeling and the possibility of future targeted therapy.
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland. Electronic address: phassoun@jhmi.edu.
authors: Paul M
authors: PM
authors: Hassoun
authors: Department of Internal Medicine, Cochin Hospital, Paris-Descartes University, Paris, France.
authors: Luc
authors: L
authors: Mouthon
authors: Servei de Pneumologia, Hospital Clinic, Universitat de Barcelona, and CIBERES, Barcelona, Spain.
authors: Joan A
authors: JA
authors: Barberà
authors: Departement de Physiologie, Hôpital Henri Mondor, Créteil, France.
authors: Saadia
authors: S
authors: Eddahibi
authors: Division of Pulmonary Sciences & Critical Care Medicine, University of Colorado, Denver, Colorado.
authors: Sonia C
authors: SC
authors: Flores
authors: Medical Clinic IV and V, University Hospital Giessen and Marburg GmbH, Giessen, Germany.
authors: Friedrich
authors: F
authors: Grimminger
authors: University of Pennsylvania, Penn/CMREF Center for Pulmonary Arterial Hypertension Research, Philadelphia, Pennsylvania.
authors: Peter Lloyd
authors: PL
authors: Jones
authors: Section of Hematology/Oncology, Department of Medicine and Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, Illinois.
authors: Michael L
authors: ML
authors: Maitland
authors: Pulmonary Hypertension Program, University of Alberta Hospital, Edmonton, Alberta, Canada.
authors: Evangelos D
authors: ED
authors: Michelakis
authors: Pulmonary Vascular Diseases Unit, Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
authors: Nicholas W
authors: NW
authors: Morrell
authors: Department of Medicine, Division of Pulmonary/Allergy/Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: John H
authors: JH
authors: Newman
authors: The Wall Center for Pulmonary Vascular Diseases, Stanford University School of Medicine, Stanford, California.
authors: Marlene
authors: M
authors: Rabinovitch
authors: Department of Internal Medicine, Justus-Liebig University of Giessen, Giessen, Germany.
authors: Ralph
authors: R
authors: Schermuly
authors: Developmental Lung Biology Laboratory, University of Colorado at Denver and Health Sciences Center, Denver, Colorado.
authors: Kurt R
authors: KR
authors: Stenmark
authors: Pulmonary and Critical Care Division, Virginia Commonwealth University, Richmond, Virginia.
authors: Norbert F
authors: NF
authors: Voelkel
authors: Department of Medicine, University of California San Diego, La Jolla, California.
authors: Jason X-J
authors: JX
authors: Yuan
authors: Université Paris-Sud, Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine Béclère, Clamart, France.
authors: Marc
authors: M
authors: Humbert
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018946:Chemokine CCL5; D020523:Chemokines, CX3C / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology / Q000821:virology; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D050778:NFATC Transcription Factors / Q000502:physiology; D012595:Scleroderma, Systemic / Q000473:pathology / Q000503:physiopathology; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D018946:Chemokine CCL5; D020523:Chemokines, CX3C; D016207:Cytokines; D050778:NFATC Transcription Factors