Uremic Toxins Deregulate the Expression of miR-29a and miR-29b in Endothelial Cells.

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with chronic kidney disease (CKD). The uremic toxins that accumulate in CKD patients as a result of impaired kidney function are involved in vascular dysfunction and increase the already high risk of cardiovascular mortality in this population. Although recent studies suggest that dysregulation of the microRNA (miRNA)-29 family is associated with impaired vascular function, the effect of uremia on miR-29 expression in the vascular wall has yet to be characterized. To this end, we investigated the effect of uremic serum and two representative uremic toxins (inorganic phosphate (Pi) and indoxyl sulfate (IS)) on miR-29a and miR-29b expression in human umbilical vein endothelial cells (HUVECs). After 24 h and five days of treatment with ure- mic serum, there were no significant differences in miR-29a and miR-29b expression (relative to control experiments with non-uremic serum). In HUVECs, 24 h (but not five days) of incubation with IS was associated with downregulation of miR-29a and miR-29b expression. In HUVECs, five days (but not 24 h) of incubation with Pisignificantly increased the expression of both miR-29a and miR-29b. We also found those 10 weeks of CKD upregulatesmiR-29a and miR-29b in the murine aorta. Overall, our results suggest that the various uremic toxins in uremic serum (including Piand IS) are associated with both upregulation and downregulation of miR-29s in vascular walls - emphasizing the complexity of miR-29 regulation in CKD.