(844.7) Downregulation of Angiotensin Type 1 Receptor by Ferulic Acid in Rat Liver Epithelial Cells

Poster Board Number: B170

Ellen Cravens (AT Still University Kirksville College of Osteopathic Medicine), Thomas Thekkumkara (Texas Tech University Health Sciences Center School of Pharmacy), Rekha Yesudas (AT Still University Kirksville College of Osteopathic Medicine)

The renin-angiotensin system plays a key role in the regulation of cardiovascular functions through the angiotensin type-1 receptor (AT1R), particularly in the control of hypertension. Previous studies have shown that plant-derived polyphenols appear to provide protection against cardiovascular diseases. However, the target or mechanism(s) involved in the protective effects of polyphenols remains unclear. Ferulic acid is a naturally occurring plant derived polyphenol with anti-inflammatory and cardioprotective properties. We hypothesized that ferulic acid would have a pivotal role in the regulation of AT1R expression and function. In the present study, we investigated the effects of ferulic acid on AT1R expression. We used a continuously passaged rat liver epithelial cells (WB) with high levels of native AT1R expression. Cells were cultured to 80-90% confluency and exposed to ferulic acid to determine cell viability, cell count, cell size and AT1R receptor expression. Exposure of the cells to 10𝜇g/ml ferulic acid (IC50 concentration) resulted in a significant downregulation of AT1R cell surface expression (Figure). Consistent with the cell surface receptor downregulation we observed downregulation of immature AT1R protein in the cytosol, suggesting the downregulatory effect of ferulic acid is mediated through gene transcription. Under similar conditions, we observed no change in cell morphology, count, or total protein content. Cell viability assay and cell size assessment also indicated that ferulic acid treatment was not affecting the normal growth of these cells. Although further studies are needed to confirm these initial observations, our study demonstrated for the first time that ferulic acid inhibits the AT1R expression in WB cells demonstrating a role for polyphenol in hypertension control in part through AT1R downregulation. 

Support or Funding Information

A.T. Still University grant no. 200-171.



Figure: Ferulic acid inhibits cell surface expression of AT1R (representative image). Immunofluorescence studies were performed using AT1R specific antibody to determine the effects of ferulic acid on native receptor expression in WB cells. Left panel: control (untreated) and right panel (treated) 10𝜇g/ml ferulic acid for 20hr. Magnification: 40x.