Lycopene Ameliorates Transplant Arteriosclerosis in Vascular Allograft Transplantation by Regulating the NO/cGMP Pathways and Rho-Associated Kinases Expression.

Yunqiang He,Ziqiang Xu,Hao Jin,Bicheng Chen,Peng Xia,Yan Zhang

doi:10.1155/2016/3128280

Abstract

Objective. Transplant arteriosclerosis is considered one of the major factors affecting the survival time of grafts after organ transplantation. In this study, we proposed a hypothesis of whether lycopene can protect grafted vessels through regulating key proteins expression involved in arteriosclerosis. Methods. Allogeneic aortic transplantation was performed using Brow-Norway rats as donors and Lewis rats as recipients. After transplantation, the recipients were divided into two groups: the allograft group and the lycopene group. Negative control rats (isograft group) were also established. Histopathological staining was performed to observe the pathological changes, and the expression levels of Ki-67, caspase-3, Rho-associated kinases, intercellular adhesion molecules (ICAM-1), and eNOS were assessed. Western blotting analysis and real-time PCR were also performed for quantitative analysis. Results. The histopathological staining showed that vascular stenosis and intimal thickening were not evident after lycopene treatment. The Ki-67, ROCK1, ROCK2, and ICAM-1 expression levels were significantly decreased. However, eNOS expression in grafted arteries and plasma cGMP concentration were increased after lycopene treatment. Conclusions. Lycopene could alleviate vascular arteriosclerosis in allograft transplantation via downregulating Rho-associated kinases and regulating key factor expression through the NO/cGMP pathways, which may provide a potentially effective method for transplant arteriosclerosis in clinical organ transplantation.

Highlights

Significant advances in the application of immunosuppressants have significantly increased the success rate of organ transplantation [1], transplant arteriosclerosis (TA) is considered as one of the major causes of graft failure in a number of transplant patients [2]
The results of our study demonstrated that intimal hyperplasia and smooth muscle cell proliferation were remarkably reduced by the administration of lycopene at 8 weeks after allogeneic aortic transplantation
We found that lycopene could increase the expression of PKG-I and eNOS, downregulate the expression of ROCK1, ROCK2, and ICAM-1, and inhibit the infiltration of inflammatory cell in allograft vessels

Summary

Introduction

Significant advances in the application of immunosuppressants have significantly increased the success rate of organ transplantation [1], transplant arteriosclerosis (TA) is considered as one of the major causes of graft failure in a number of transplant patients [2]. Vessel protection in grafts has been considered crucial treatment after organ transplantation, which will effectively prevent the occurrence of transplant arteriosclerosis [4]. Lycopene is a natural carotenoid that exists in tomatoes and tomato products. It is considered as one of the most effective singlet oxygen species in carotenoids [5]. It is widely known that lycopene can maintain the normal function of the vascular endothelium by regulating

Methods

Results

Conclusion