Background: Treatment with isotretinoin (13-cis-retinoic acid; 13-cis RA) has been associated with hypertriglyceridemia and low levels of high-density lipoprotein (HDL)-cholesterol, which are well-established cardiovascular risk factors. The development of hypertriglyceridemia secondary to this treatment could predispose to the metabolic syndrome. Hence, because of the risk of atherosclerosis associated with this treatment and to help unravel the underlying mechanisms involved, we studied the effect of 13-cis RA on genetic expression in endothelial cells.
Methods: Total RNA was isolated from human umbilical vein endothelial cells (HUVECs) treated without 13-cis RA (control) or incubated with 13-cis RA (1 microM) for 6 and 24 h. Microarray analysis (Affymetrix U133A array) with >22,000 probes was used with real time RT-PCR of a series of genes selected because of their involvement in the RA signaling pathway.
Results: The treatment of endothelial cells with 13-cis RA produced significant changes in the expression of genes implicated in cell adhesion and in lipid metabolism processes, specifically in the clearance of lipoprotein remnant particles and in HDL metabolism.
Conclusions: Isotretinoin in the endothelium has an exacerbating effect on atherosclerosis risk factors. This is especially relevant in the regulation of expression of genes involved in the processes of cell adhesion and lipid metabolism.