Gene Expression Profile of HCAEC Cells Exposed to Serum From Chronic Kidney Disease Patients: Role of MAPK Signaling Pathway

Abstract End-stage renal disease (ESRD) patients have an elevated risk of cardiovascular (CV) complications including acute myocardial infarction (AMI); endothelial dysfunction and accumulation of uremic toxins have been associated with such CV-events. To explore which molecular pathways are involved in this CV-complication and the effects of the uremic serum on gene expression, an endothelial dysfunction model was studied through microarrays and pathway analysis. mRNA was isolated of human coronary arterial endothelial cells (HCAEC) primary cultures supplemented with 20% uremic serum from two groups of patients, USI: ESRD-patients; UCI: ESRD-AMI-patients. Affymetrix GeneChip® microarray and the LIMMA-package (Linear Models for Microarray Data) of the Bioconductor sofware17 was implemented to identify relevant DEGs between the two groups of uremic patients. Protein-protein interaction networks and pathway analysis were made to analyze the interaction and expression tendency of differentially expressed genes. 100 differentially expressed genes were identified from two data sets triggered by uremic state using bioinformatics, from 16,607. After in a new cohort, 30 genes were overexpressed in UCI group, which we identified 500 ontological genetic terms and one KEGG-pathway with p < 0.05. The metabolic pathway significantly represented was the MAPK signaling pathway. Network analysis showed six genes (PTGS2, SELE, ICAM1, HMOX1, EGR1, and TLR2) that represent potential markers for ESRD with AMI, as an approximation to their underlying mechanisms. The results obtained suggest that uremic toxins in patients with ESRD can alter HCAEC and modify the gene expression profile, which could have an impact on the development of cardiovascular complications in these patients.