Faculty Collaboration Database

FK409, a spontaneous nitric oxide releaser, attenuates allograft vasculopathy in a rat aortic transplant model. Circ Res 2000 Jul 07;87(1):66-72

Date

07/08/2000

Pubmed ID

10884374

DOI

10.1161/01.res.87.1.66

Scopus ID

2-s2.0-0034617060 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

Although systemic administration of NO donors has been shown to attenuate the development of neointimal hyperplasia in the balloon injury model, this strategy has not been tested in a model of allograft vasculopathy. In this study, we investigated the effect of FK409, a spontaneous NO releaser, on the development of allograft vasculopathy, using a rat aortic transplant model. Thoracic aortas from ACI rats were transplanted heterotopically into the abdominal aorta of Wistar-Furth rats. Postoperatively, recipients received FK409 orally every 8 hours from the day of transplantation to the time of euthanization. Morphometric and immunohistochemical analyses were performed on the aortic grafts 8 weeks after transplantation. Control allografts showed severe neointimal hyperplasia, which consists mainly of alpha-actin-containing vascular smooth muscle cells. The FK409-treated allografts showed a dose-dependent reduction (statistically significant compared with the control) in the neointimal thickness as the dose increased from 1 to 10 mg/kg (thrice per day). However, there was no significant difference in the neointimal thickness between groups treated with 10 and with 20 mg/kg. FK409 treatment (10 mg/kg) caused a significant decrease in DNA synthesis (5-bromo-2-deoxyuridine [BrdU] uptake), an increase in DNA fragmentation (terminal deoxynucleotidyltransferase-mediated uridine nick-end labeling [TUNEL]), and upregulation of Fas expression, in the neointimal vascular smooth muscle cells. These data suggest that FK409 attenuates the allograft vasculopathy in a rat aortic transplant model.

Author List

Fukada J, Schena S, Tack I, Ruiz P, Kurimoto Y, Pang M, Aitouche A, Abe T, Striker LJ, Pham SM

Author

Stefano Schena MD, PhD Associate Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Aorta
Apoptosis
Bromodeoxyuridine
Cyclosporine
Immunohistochemistry
Male
Muscle, Smooth, Vascular
Nitric Oxide Donors
Nitro Compounds
Rats
Rats, Inbred ACI
Rats, Inbred WF
Transplantation, Homologous