title: Circulating soluble receptor for advanced glycation end products (sRAGE) as a biomarker of emphysema and the RAGE axis in the lung.
abstract: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease that has been traditionally characterized by incompletely reversible airflow limitation. Yet, the latter is poorly correlated with many other clinically relevant characteristics of the disease. Thus, the identification of biomarkers to more accurately assess this heterogeneity and disease severity may facilitate the discovery and development of new treatments and better management of patients with COPD. One molecule that has attracted attention as a potentially useful biomarker specifically for the emphysema subpopulation is the soluble receptor for advanced glycation end products (sRAGE). As the soluble isoform of a key proinflammatory signaling receptor, sRAGE acts as a "decoy" for RAGE ligands and prevents their interaction with the receptor. Multiple reports have now linked sRAGE to COPD, and more specifically to emphysema, and evidence is accumulating that this link is likely mechanistic in nature. Here we review the current state of knowledge about sRAGE biology, the mechanistic links to COPD, and the evidence for using it as a biomarker for emphysema. We also discuss sRAGE as a potential target for therapeutic intervention in COPD.
authors.affiliation: 1 GlaxoSmithKline Research and Development, King of Prussia, Pennsylvania.
authors.forename: John G
authors.initials: JG
authors.lastname: Yonchuk
authors.affiliation: 2 Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.affiliation: 3 National Jewish Health, Denver, Colorado.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.affiliation: 4 Thorax Institute, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Barcelona, Spain; and.
authors.forename: Alvar
authors.initials: A
authors.lastname: Agustí
authors.affiliation: 5 Wolfson Institute for Biochemical Research, Division of Medicine, University College London, London, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.affiliation: 1 GlaxoSmithKline Research and Development, King of Prussia, Pennsylvania.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Miller
authors.affiliation: 1 GlaxoSmithKline Research and Development, King of Prussia, Pennsylvania.
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.affiliation: 1 GlaxoSmithKline Research and Development, King of Prussia, Pennsylvania.
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Mayer
mesh_terms: D015415:Biomarkers / Q000097:blood*; D055106:Genome-Wide Association Study; D006801:Humans; D008168:Lung / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood*
chemical_list: D015415:Biomarkers; D000067759:Receptor for Advanced Glycation End Products
keywords: biomarker; chronic obstructive pulmonary disease; emphysema; soluble receptor for advanced glycation end products