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

Vejlstrup, Niels G; Andersen, Claus B; Boesgaard, Søren; Mortensen, Svend A; Aldershvile, Jan

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 21, Issue 2 , Pages 211-216, February 2002

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

Niels G Vejlstrup, MD, PhD
- Reprint requests: Niels G Vejlstrup, MD, Medical Department B 2142, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark Telephone: +45-35-45-23-47. Fax: +45-35-45-25-13
- Medical Department B, Division of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Claus B Andersen, MD, PhD
- Medical Department B, Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Søren Boesgaard, MD, PhD,
- Medical Department B, Division of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Svend A Mortensen, MD, PhD,
- Medical Department B, Division of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Jan Aldershvile, MD, PhD
- Medical Department B, Division of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Received 30 April 2001; accepted 16 July 2001.

Abstract

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.