The role of Mineralocorticoid Receptor on Human Aortic Endothelial Ion Channel Expression Profile in Chronic Kidney Disease

Abstract

Patients with chronic kidney disease (CKD) have a markedly increased incidence of cardiovascular events and cardiovascular disease (CVD) mortality compared with the age-matched general population. The high concentration of circulating uremic toxins in CDK patients may trigger vascular inflammatory responses, thereby inducing endothelial dysfunction, which is associated with CVD development and progression. In addition, plasma aldosterone levels are increased in CKD, and aldosterone has been found to increase vascular inflammation and fibrosis. The aim of our study was to analyze the influence of CKD in the expression of endothelial ion channels and its potential modification by mineralocorticoid receptor (MR) antagonism, which would consequently affect endothelial dysfunction. To that end we used human aortic endothelial cells (HAEC) cultured in medium supplemented with pooled sera from either healthy or uremic patients undergoing dialysis, as well as both groups in the presence of spironolactone. HAEC were found to express MR under the culture conditions used. To obtain a global portrait of ion channel expression in HAEC in the four groups tested, we performed high-throughput real-time polymerase chain reaction of 92 ion channel genes using a custom-designed Taqman low-density array card. We have obtained a profile of ion channel gene expression altered by uremic serum and the effect of spironolactone both on basal and altered expression of ion channel subunits.