RT Journal Article
SR Electronic
T1 Alterations in gene expression of RAGE and its sheddases in blood of COPD patients do not relate to decreased plasma (e)sRAGE levels
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P3950
VO 44
IS Suppl 58
A1 Poornima Gopal
A1 Erica Rutten
A1 Frits Franssen
A1 Emiel Wouters
A1 Niki Reynaert
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P3950.abstract
AB Plasma sRAGE levels are decreased in COPD, correlating with airflow limitation and emphysema. sRAGE originates from alternative splicing (esRAGE) and cleavage by ADAM10 and MMP9, and acts as a decoy receptor limiting pro-inflammatory signalling. The current study evaluated gene expression of RAGE and its sheddases in circulating cells and their relation with plasma (e)sRAGE levels in COPD.The study included 160 COPD patients, 79 smoking and 41 never smoking age-matched control subjects. Full lung function was assessed and gene expression of total, membrane and esRAGE and sheddases was determined in circulating white blood cells by QPCR. Plasma levels of sRAGE and esRAGE were measured by ELISA.Total RAGE gene expression was decreased in COPD, whereas membrane and esRAGE expression was unaffected. Expression of the sheddase ADAM10 was decreased while MMP9 expression increased. Decreased plasma levels of sRAGE and esRAGE were found in COPD patients compared to smoking and never-smoking controls, and total plasma sRAGE, but not esRAGE correlated with lung function (FEV1 β=0.314, p‹0.001), DLCO (β=0.197, p=0.016), and emphysema severity (β=-0.273, p=0.001). No significant associations of gene expression of RAGE or its sheddases to plasma (e)sRAGE levels were observed.This study confirms the potential of plasma sRAGE as a biomarker of lung function and emphysema in COPD. Despite observed alterations in expression of RAGE and its sheddases in white blood cells in COPD, decreased sRAGE levels in the circulation are likely not attributable to these changes. Pulmonary RAGE expression and shedding should therefore be examined in parallel with plasma sRAGE.