Proteomic analysis of vascular access in patients with chronic kidney disease at stage 5 / 西安交通大学学报(医学版)

ABSTRACT

Objective: By applying the proteomic method, to analyze differences of protein expressions and signal pathways in veins at arteriovenous fistula in chronic kidney disease stage 5 (CKD5) patients with or without diabetes so as to explore the pathogenesis of high incidence of arteriovenous fistula functional incapacitation in CKD5 patients with diabetes. Methods: The protein expression RAW datasets of vascular access from CKD5 patients with or without diabetes in Proteomexchange Database were screened out and downloaded. Then the identified features were searched from UniProt/SwisssProt human proteins database through the software ProteomeDiscovery (PD). Then, the PD generated a file of quantitative proteins data. The significantly different proteins between two groups were screened out and analyzed by T-test or Adj T-test depending on homogeneity of variance. These significantly different proteins were enriched into different biological pathways through IPA analysis, GO enrichment analysis, and KEGG pathway analysis, which signifies these biological pathways are significantly different. Ultimately, the correlation of proteins in different biological pathway was analyzed by Spearman correlation test. Results: TheiTRAQ labeled proteins RAW datasets comparing the vessels from CKD5 patients with diabetes and without diabetes (PXD010883) were collected at first. After searching identified features again and disposing the data, a total of 120 significantly different proteins including 89 up-regulated proteins and 31 down-regulated proteins were screened out finally. Through GO, KEGG and IPA analyses, there were two significantly different biological pathways. On the one hand, the purine nucleoside monophosphate metabolic change and the ratio of ATP/AMP decrease were reflected in oxidative phosphorylation receding and AMP metabolism enhancing in CKD5 patients with diabetes. On the other hand, the muscle system process which played a vital role in VSM cells receded in CKD5 patients with diabetes. It was specific in the decrease of MYH11, CNN1 and so on. Excitingly, the significantly differential genes in the two pathway had a strong correlation. The results explained why CKD5 patients with diabetes always have cardiovascular disease. Conclusion: The ratio of ATP/AMP reduction caused by diabetes led to muscle function disorder of VSM cells, which explains the reason for the internal fistula functional incapacitation in CKD5 patients with diabetes.