Effect of rapamycin on formation of atherosclerosis induced by AGEs in renal transplantation recipients and mechanism

Abstract

Objective +o investigate the inhibitory effect of sirolimus on formation of atherosclerosis (AS) induced by advanced glycation end products (AGE) in kidney transplantation recipients and mechanism.Method Five cases of definite diagnosis of AS were included.Structural changes of renal transplant vascular tissues were observed before and after the application of sirolimus for at least over 1 year once the definite diagnosis of AS was made by transplant kidney aspiration biopsy.SD rat aortic smooth muscle cells (VSMC) were isolated and cultured in vitro and identified by immunofluorescence staining.Sirolimus group (sirolimus culture),AGE group (AGE culture),experimental group (sirolimus and AGE co-culture) and control group (bovine serum albumin culture) were established.VSMCs of the 5th generation from each group were collected and the expression levels of α-smooth muscle actin (α-SMA),osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) were detected by Western blotting.Result Significant thickness was found in the media layer of vessels in allograft kidney from recipients with AS comparing with significant attenuation after the administration of sirolimus for 13.0 + 1.8 months.+he in vitro experiments showed that α-SMA was overexpressed in both 2 nd and 5 th generation VSMCs of normal SD rats; in contrast,low expression of α-SMA and high expression of OPN and PCNA were detected after the exposure of AGE (P＜ 0.05).Moreover,as compared with AGE group,PCNA and OPN were significantly decreased,and α-SMA was significantly increased in experimental group (P＜0.05).Conclusion Sirolimus can inhibit the progression of post-transplant AS induced by AGE possibly through suppressing the proliferation of VSMCs and transdifferentiation of their phenotypes. Key words: Kidney transplantion; Sirolimus ; Artherosclerosis; AGE