Temporal changes in myocardial endothelial nitric oxide synthase expression following human heart transplantation.
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.


CONCLUSIONS
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.
Vejlstrup
Niels G
NG
Medical Department B, Division of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Vejlstrup@dadlnet.dk
Andersen
Claus B
CB
Boesgaard
Søren
S
Mortensen
Svend A
SA
Aldershvile
Jan
J
D000328:Adult; D001706:Biopsy; D002675:Child, Preschool; D003718:Denmark; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D013699:Temporal Arteries / Q000201:enzymology* / Q000473:pathology
D019001:Nitric Oxide Synthase