Details

Autor(en) / Beteiligte

• Holweg, Cecile T.J.
• Balk, Aggie H.M.M.
• Snaathorst, Jasper
• van den Engel, Sandra
• Niesters, Hubert G.M.
• Maat, Alex W.P.M.
• Zondervan, P.E.
• Weimar, Willem
• Baan, Carla C.

Titel

Intragraft heme oxygenase-1 and coronary artery disease after heart transplantation

Ist Teil von

• Transplant immunology, 2004-12, Vol.13 (4), p.265-272

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2004

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Peri-operative tissue injury triggers the development of Transplant Coronary Artery Disease (TCAD). Animal studies have shown that induction of heme oxygenase (HO)-1 protects the donor organ from the development of TCAD. To investigate the role of HO-1 in TCAD after clinical heart transplantation, we measured intragraft mRNA expression of HO-1, HIF-1α, TGF-β, FLIP, and the Bcl-2/Bax balance. Immunohistochemical staining of HO-1 was performed to determine its origin. Myocardial biopsies taken at the end of the transplantation procedure (time 0), at 1 week and at 10 months after transplantation were studied from recipients with or without angiographic signs of accelerated TCAD, diagnosed after 1 year. At time 0, no differences in mRNA expression for any of the measured parameters were found between TCAD positive and negative patients. At 1 week, mRNA expression of HO-1 and TGF-β was higher in grafts that developed accelerated TCAD ( p=0.001 and p=0.0002). These higher mRNA levels were accompanied by a pro-apoptotic shift in Bcl-2/Bax ( p=0.02), suggesting proneness for apoptosis via the mitochondrial pathway. Immunohistochemical staining showed that HO-1 was mainly produced by infiltrating macrophages. At 10 months, again HO-1 and TGF-β levels were high in TCAD positive patients ( p=0.02 and p=0.05), but the expression of apoptotic markers was comparable at this time point. Our results suggest that a higher HO-1 by macrophages in our patient population might be an adaptive response to tissue injury and inflammation, reflecting damage due to the transplantation procedure that finally results in TCAD.