Angiotensin receptors as sensitive markers of acute bronchiole injury after lung transplantation.

Abstract

Although lung transplantation is the only means of survival for patients with end-stage pulmonary disease, outcomes from this intervention are inferior to other solid organ transplants. The reason for the poor outcomes may be linked to an early reaction, such as primary graft dysfunction, and associated with marked inflammatory response, bronchiole injury, and later fibrotic responses. Mediators regulating these effects include angiotensin II and matrix metalloproteinases (MMPs). We investigated changes to these mediators over the course of cardiopulmonary bypass (CPB) and up to 72 h after lung transplantation, using immunohistochemistry, Western blot, and ELISA techniques. We found 4- and 16-fold increases in plasma angiotensin II and MMP-9, respectively, from pre-CPB to post-CPB. MMP-9 levels remained elevated 1 h after transplantation. MMP-2 levels were elevated 6-24 h after lung transplantation. Type 2 angiotensin II receptor (ATR2) expression was 3.5-fold higher in bronchoalveolar cells 1-6 h after transplantation than in controls. The study suggests that the combination of cardiopulmonary bypass and lung transplantation is associated with early changes in the angiotensin II receptor system and in MMPs, and that altered expression of these mediators may be a useful marker to examine pathological changes that occur in lungs during transplant surgery.