RT Journal Article
SR Electronic
T1 Prostacyclin and VEGF in the rejection process after lung transplantation – A possible biomarker
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA4040
DO 10.1183/13993003.congress-2016.PA4040
VO 48
IS suppl 60
A1 Andersson Sjoland, Annika
A1 Larsson Callerfelt, Anna-Karin
A1 Thiman, Lena
A1 Hallgren, Oskar
A1 Skog, Ingrid
A1 Hansson, Lennart
A1 Eriksson, Leif
A1 Bjermer, Leif
A1 Westergren-Thorsson, Gunilla
YR 2016
UL https://publications.ersnet.org//content/48/suppl_60/PA4040.abstract
AB Many lung-transplanted (LTx) patients develop obliterative bronchiolitis (OB) with deposition of extracellular matrix, accompanied by fibrocyte infiltration and increased lumen of vessels. In this study we hypothesize that fibrocytes, VEGF and prostacyclin (PGI2) are involved in remodelling processes after LTx. We investigated TGF-β activated peripheral fibroblast phenotypes regarding production of VEGF165/PGI2. Fibrocytes and fibroblast phenotypes were identified by prolyl4-hydroxylase (p4OH), CD45, VEGFR2 or PGIR. VEGF production from fibroblasts after LTx significantly decreased 3mo after LTx compared to healthy controls (p<0.05). Fibroblasts from patients that had developed OB produced significant more VEGF after TGF-β stimulation compared to patients without BOS (p<0.05). The production of VEGF was negatively correlated with migratory properties of fibroblast (R-0.81, p<0.05). PGI2 synthesis was increased in LTx 6mo compared to 3mo postTPx (p<0.05) and controls (p<0.05). In a more detailed case study of 3 pat, two with and one without OB, the altered production of VEGF/PGI2 was associated with OB development. Both the number of fibroblasts expressing p4OH/VEGFR2 and p4OH/PGIR were increased in patients with OB compared to healthy controls (p<0.05). The number of p4OH/VEGFR2 fibroblasts correlated with lumen area of vessels (R0.80 p<0.001). Number of fibrocytes was correlated with fibroblasts expressing p4OH/VEGFR2 (R0.63 p<0.01). Remodelling of both the vascular and respiratory compartment plays an important role in the rejection process after LTx. Our results suggest that fibrocytes, PGI2/R and VEGF/R2 are altered and may contributeto the rejection process after LTx.