Lipid and Oxidative Stress Disorders in a Rat Model of Chronic Rejection

Abstract: Chronic allograft dysfunction is the primary cause of graft loss after the first posttransplant year. Graft arteriosclerosis, a main component of this pathology, has oxidative stress and interactions with lipid disorders as part of the pathogenesis. The objective of our study was to determine whether oxidative stress was associated with the vascular lesions observed in a rodent model of graft arteriosclerosis. Using model of orthotopic aortic allograft in the rat, the allotransplantation (A) group included 12 Sprague-Dawley donors to 12 Lewis recipients, and the isotransplantation (B) group. 12 Lewis donors to 12 Lewis recipients. The rats received no immunosuppressants or antioxidants. After 12 weeks, the rats were humanely killed and the aorta cryopreserved until analysis. Blood samples were drawn for lipid assessment and oxidative stress analysis. Tissue expression of NADPH oxidase was quantified by Western blot, determining the constitutive membrane unit (p22phox) and the cytosolic regulating unit (p67phox). We observed a greater increase in the plasma markers of oxidative stress in group A than group B but without lipid abnormalities. The expression of NADPH subunits p22phox and p67phox were similar in both groups. These results showed that oxidative stress was associated with vascular lesions in our aortic graft model, but the origin of oxidative stress seemed to be independent of the NADPH oxidase. [Copyright &y& Elsevier]