Inhibition of chronic rejection of aortic allografts by dietary glycine.
BACKGROUND
Chronic rejection is influenced by a variety of risk factors, including histoincompatibility and ischemia. Glycine, a cytoprotective agent, has been shown to protect against ischemia-reperfusion injury in the liver, inactivate hepatic resident macrophages, minimize cyclosporin A-induced nephrotoxicity, and exhibit immunosuppressive properties in vitro. The aim of this study was to investigate whether dietary glycine could reduce development of chronic rejection.


METHODS
Lewis recipients of Fisher-344 abdominal aortic allografts received diets that contained either 5% glycine plus 15% casein or 20% casein as control for 10 weeks. Vascular lesions of aortic isografts and allografts were evaluated quantitatively with image analysis and cell counting.


RESULTS
No significant vascular changes were observed in isografts (mean medial areas of 3.3 +/- 0.3x0(5) microm2). However, dramatic intimal thickening (neointimal area 2.1+/-0.3) and medial thinning (1.5+/-0.3) were observed in allografts from rats fed control diet. In contrast, glycine significantly reduced the neointima by 45% (1.2+/-0.3) and protected the media (3.5+/-0.2). This led to intima to media area ratios almost twice as large in the control group as in glycine-fed rats (2.2+/-0.4 vs. 1.1+/-0.3, P<0.05). Moreover, infiltrating leukocytes, especially macrophages, were reduced significantly in the adventitia by glycine. In addition, glycine inhibited proliferation and migration of rat aortic smooth muscle cells in culture by 45 and 60%, respectively.


CONCLUSIONS
These results indicate that dietary glycine minimizes histopathological changes of chronic rejection by reducing the immune response and, in part, by minimizing proliferation and migration of smooth muscle cells.
Yin
M
M
Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7365, USA.
Rusyn
I
I
Schoonhoven
R
R
Graves
L M
LM
Rusyn
E V
EV
Li
X
X
Li
F
F
Cox
A D
AD
Harding
T W
TW
Bunzendahl
H
H
Swenberg
J A
JA
Thurman
R G
RG
D000818:Animals; D001011:Aorta / Q000601:surgery; D001012:Aorta, Abdominal / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D004032:Diet; D005260:Female; D005998:Glycine / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D007962:Leukocytes / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D017539:Tunica Intima / Q000378:metabolism
D018809:Proliferating Cell Nuclear Antigen; D005998:Glycine