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Temporal changes in myocardial endothelial nitric oxide synthase expression following human heart transplantation
Niels G Vejlstrup1, Claus B Andersen, Søren Boesgaard
1Medical Department B, Division of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Vejlstrup@dadlnet.dk
Background:
The incidence of cardiac allograft vasculopathy increases with time after heart transplantation. Allograft vasculopathy is associated with endothelial dysfunction and reduced endothelium-dependent nitric oxide-mediated vascular effects. In this study, temporal changes in endothelial nitric oxide synthase (NOS3) expression in human myocardial biopsies were investigated during the first 3 years after heart transplantation.
Methods:
In each patient (n = 7), the immunohistochemical presence of NOS3 and inducible nitric oxide synthase were examined in serial biopsies taken at 1, 4, and 26 weeks and at 1, 2, and 3 years after transplantation.
Results:
Endothelial nitric oxide synthase was present in vascular endothelial cells in all biopsies at the time of transplantation. A rapid fall within the first months in the number of NOS3-positive biopsies was observed, with a possible difference in the rate of disappearance among the capillaries, the arterial endothelium, and the venous endothelium. After 2 years, very little NOS3 could be detected. Inducible nitric oxide synthase was present in vascular smooth muscle cells throughout the study period and did not change.
Conclusion:
Endothelial nitric oxide synthase immunoreactivity is gradually lost after heart transplantation. These changes may be responsible for the coronary endothelial dysfunction often seen after human cardiac transplantation.