Action of 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitors on ABCA-1 protein (ATP-Binding Cassette Transporter-1) in endothelial cells stimulated with uremic serum.

Abstract

The high incidence of cardiovascular events in chronic kidney disease (CKD) exhibits an epidemic character, affecting patients in predialysis, hemodialysis, and post-transplant stages, accounting for approximately 50% of deaths, with a mortality rate around 9% per year. Statins are primarily used in the treatment of dyslipidemia and possess pleiotropic effects that are not yet fully understood. Moreover, there is insufficient evidence to support their use in attenuating cardiovascular outcomes or their potential role in modulating the ABCA-1 transporter in CKD. Thus, the aim of this study was to investigate the effect of statins on ABCA-1 modulation in cultures of human umbilical vein endothelial cells (HUVEC) incubated with uremic serum from CKD patients. The results demonstrate that statins influence the inflammatory response of HUVEC exposed to a uremic environment by reducing TNF-α secretion compared to baseline levels. Furthermore, the uremic environment was found to decrease the expression of LxR-β and RxR-α, leading to a consequent reduction in ABCA-1 expression in HUVEC. Cells pre-treated with simvastatin exhibited increased expression of ABCA-1, LxR-β, and RxR-α, along with a significant increase in the transcription of ABCA-1, LXR-β, and RxR-α, indicating that statins may exert a positive modulation on LxR-β and RxR-α receptors, activating ABCA-1 transcription.