Abstract: FR-PO1023
Action of 3-Hydroxymethylglutaryl CoA Reductase Inhibitors on ABCA-1 Protein (ATP-Binding Cassette Transporter-1) in Endothelial Cells Stimulated with Uremic Serum
Session Information
- CKD Mechanisms: From Mendel to Mars
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Batista, Marcelo Costa, Universidade Federal de Sao Paulo, São Paulo, Sao Paulo, Brazil
- Quinto, Beata M r, Universidade Federal de Sao Paulo, São Paulo, Sao Paulo, Brazil
Background
High incidence of cardiovascular events in chronic kidney disease (CKD) presents an epidemic character, including patients on predialysis, hemodialysis and post-transplant patients covering about 50% of deaths, with a mortality rate around 9% per year. The statins have been used primarily in the treatment of dyslipidemia and have pleiotropic effects not fully elucidated, as well as, there is no evidence to support its use for attenuation of the cardiovascular outcome and its potential action on ABCA-1 transporter modulation in DRC.
Thus, our aim was to verify the effect of statins on ABCA-1 modulation in cells culture of human umbilical vein (HUVEC) incubated with uremic serum from CKD patients.
Methods
Human umbilical cord vein endothelial cells (HUVEC) were pretreated with simvastatin and incubated with uremic serum. All groups were incubated for 24 hours at 37oC, under ideal conditions of humidity and CO2 concentration.
Expression of LxR α, LxRβ, RxR-α, and ABCA-1 was performed by real-time PCR, the levels of Interleukin 10 and TNF-α in the cell supernatant were measured by enzyme immunoassay, using the ELISA kit. Transfection of HUVEC cells was performed for analysis of promoter activation mediated by LxR and RxR-reporter gene and the expression of LxRβ, RxRα and ABCA1 evaluated by Western Blott.
Results
We demonstrate that statins act on the inflammatory response of HUVEC cells exposed to the uremic environment by decreasing TNF-α secretion when compared to basal secretion. Our results suggest that the uremic environment reduces the expression of LxR-β and RxR-α leading to a consequent decrease in ABCA-1 expression in HUVEC. Pretreatement of endothlial cellwith simvastatin showed increased expression of ABCA-1, LxR-β and RxR-α, as well as the transcription of ABCA-1, LXR-β and RxR-α was significantly increased,
Conclusion
Our results suggests that statins may exert positive modulation on the LxR-β and RxR-α receptors for ABCA-1 transcription activation.
Funding
- Government Support – Non-U.S.