Inhibition of chronic rejection of aortic allografts by dietary glycine

Background, Chronic rejection is influenced by a variety of risk factors, i ncluding histoincompatibility and ischemia, Glycine, a cytoprotective agent , has been shown to protect against ischemia-reperfusion injury in the live r, 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 devel opment of chronic rejection. Methods. Lewis recipients of Fisher-344 abdominal aortic allografts receive d diets that contained either 5% glycine plus 15% casein or 20% casein as c ontrol for 10 weeks, Vascular lesions of aortic isografts and allografts we re evaluated quantitatively with image analysis and cell counting. Results, No significant vascular changes were observed in isografts (mean m edial areas of 3.3+/-0.3x0(5) mu m(2)). However, dramatic intimal thickenin g (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 significant ly 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). M oreover, infiltrating leukocytes, especially macrophages, were reduced sign ificantly in the adventitia by glycine, In addition, glycine inhibited prol iferation and migration of rat aortic smooth muscle cells in culture by 45 and 60%, respectively. Conclusion. These results indicate that dietary glycine minimizes histopath ological changes of chronic rejection by reducing the Immune response and, in part, by minimizing proliferation and migration of smooth muscle cells.