Decreased transplant arteriosclerosis in endothelial nitric oxide synthase-deficient mice.
BACKGROUND
Occlusive vascular changes, characterized by the formation of a neointima with lumen obstruction, are key histologic findings of allograft arteriosclerosis. Vascular integrity of the graft is critically dependent on nitric oxide (NO), synthesized by NO synthases (NOS), of which three isoforms have been located in the arterial wall: endothelial NOS (eNOS), inducible NOS, and neuronal NOS (nNOS). We have studied the role of NOS in a murine model of aortic allograft rejection.


METHODS
The descending thoracic aorta of donor mice (BALB/c mice) was transplanted into two groups of recipients: (a) C57BL/6J and (b) C57BL/6J mice homozygous (-/-) for a knockout of the eNOS gene (eNOS(-/-)).


RESULTS
After 4 weeks, pronounced neointima formation, upregulated expression of adhesion molecules, and increased infiltration by inflammatory cells were demonstrated in wild-type recipient mice, whereas eNOS(-/-) recipient mice were protected from neointima development by a significantly increased synthesis of NO, as shown by increased formation of cGMP; this was mainly explained by upregulation of inducible NOS and nNOS.


CONCLUSIONS
Upregulation of inducible NOS and nNOS isoforms may be beneficial in preventing allograft arteriosclerosis in the early posttransplant period.
Zebger-Gong
Hong
H
Department of Pediatric Nephrology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Kampmann
Jan
J
Kong
Linghua
L
Roigas
Jan
J
Sommer
Kerstin
K
Hoff
Uwe
U
Krämer
Stephanie
S
Peters
Harm
H
Müller
Dominik
D
Dragun
Duska
D
Querfeld
Uwe
U
D000818:Animals; D001013:Aorta, Thoracic / Q000637:transplantation*; D001161:Arteriosclerosis / Q000517:prevention & control*; D002448:Cell Adhesion; D002455:Cell Division; D006152:Cyclic GMP / Q000378:metabolism; D017931:DNA Primers; D006720:Homozygote; D007668:Kidney / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009206:Myocardium / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency* / Q000235:genetics; D011183:Postoperative Complications / Q000517:prevention & control; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017539:Tunica Intima / Q000473:pathology
D017931:DNA Primers; D009569:Nitric Oxide; D012313:RNA; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP