Effect of sirolimus on arteriosclerosis induced by advanced glycation end products via inhibition of the ILK/mTOR pathway in kidney transplantation recipients

To investigate the effect and related mechanism of sirolimus (SRL) in arteriosclerosis(AS) induced by advanced glycation end products (AGEs) in kidney transplantation recipients (KTRs). Human kidney tissues from KTRs before and after treatment with SRL were assessed by hematoxylin-eosin and immunohistochemical staining. Rat vascular smooth muscle cells (VSMCs) were treated with AGEs and/or SRL. The expressions of alpha-smooth muscle actin (alpha-SMA), osteopontin (OPN), actinin-associated LIM protein (ALP), proliferating cell nuclear antigen (PCNA), integrin-linked kinase (ILK) and the mTOR signaling pathway proteins were examined using western blot assay. Cytosolic calcium present in VSMCs was also measured by the calcium assay kit and von Kossa staining assay. The expression of alpha-SMA was remarkably higher while OPN expression was significantly lower in recipients with AS after they were administered SRL. Rat VSMCs treated with AGEs exhibited significantly lower expression of alpha-SMA and overexpression of OPN, ALP and PCNA than the other groups. In contrast, the expression of alpha-SMA was significantly higher while the expression of OPN, ALP and PCNA was significantly lower in VSMCs treated with both AGEs and SRL. Moreover, the ILK/mTOR signaling pathway was activated in rat VSMCs treated with AGEs, while treatment with AGEs and SRL led to significant inhibition of the ILK/mTOR signaling pathway. AGEs play a critical role in the development and progression of AS after kidney transplantation, but SRL can reverse these effects and therefore slow down the development of AS through inhibition of the ILK/mTOR signaling pathway.