PT - JOURNAL ARTICLE AU - Annika Andersson Sjöland AU - Lena Thiman AU - Ingrid Skog AU - Lennart Hansson AU - Leif Eriksson AU - Leif Bjermer AU - Gunilla Westergren-Thorsson AU - Anna-Karin Larsson Callerfelt TI - Elevated levels of prostacyclin and VEGF in the rejection process after lung transplantation DP - 2013 Sep 01 TA - European Respiratory Journal PG - 368 VI - 42 IP - Suppl 57 4099 - http://erj.ersjournals.com/content/42/Suppl_57/368.short 4100 - http://erj.ersjournals.com/content/42/Suppl_57/368.full SO - Eur Respir J2013 Sep 01; 42 AB - Background: Many lung-transplanted (LTx) patients develop bronchiolitis obliterans syndrome (BOS) with characteristic extracellular matrix in the bronchioles. The increased production of matrix molecules is accompanied with increased alveolar tissue and lumen area of vessels in patients with histologically characterized rejection, obliterative bronchiolitis (OB). In this study we hypothesize that vascular endothelial growth factor (VEGF) and prostacyclin (PGI2) are involved in the rejection processes with accompanied vessel remodelling after LTx. We investigated fibroblast phenotypes regarding production of VEGF/PGI2 and expression of VEGFR2/PGI receptor (R).Methods: Isolated lung fibroblasts from distal biopsies were incubated with TGF-β. PGI2, measured as 6-keto prostaglandinF1α and VEGF were analyzed in medium. Fibroblast phenotypes were identified by immunohistochemical methods by combining antibodies against prolyl 4-hydroxylase (p4OH) with VEGFR2 or PGIR in patients with OB. Vessels were identified with antibody against vWillebrand factor.Results: PGI2 expression was significantly higher in LTx compared to control subjects (p=0.02). VEGF production in patients that had developed BOS was increased 7 fold after TGF-β stimulation compared to a 2.7 fold increase in patients without BOS. Both the number of fibroblasts expressing p4OH/VEGFR2 and p4OH/PGIR were increased in patients with OB compared to healthy controls (p=0.048,p=0.024). The number of p4OH/VEGFR2 fibroblasts correlated with lumen area of vessels (R 0.80 p<0.001).Conclusions: Our results suggest that PGI2/PGIR and VEGF/VEGFR2 may contribute to the changes of vessels and fibroblast phenotype found after LTx.