In this study, we sought the use of cultured human abdominal aortic aneurysm (AAA) tissue to investigate the transcriptional effects of some bioactives, whose role in the prevention of atherosclerotic plaque development through the regulation of gene expression has been hypothesized. After supplementation with n - 3 polyunsaturated fatty acids or epigallocatechin-3-gallate, the expression of five genes involved in cholesterol metabolism was assessed in cultures of AAA tissue obtained during elective open surgery, and compared to the results obtained in a single-cell culture model (HepG2 cells). All bioactives modulated gene expression in HepG2 cells, while no effects were observed in the tissue culture due to the shortcomings of the tissue model, which showed high within-patient variations and high between-patient variations in gene expression. Results herein reported underline that the choice of the model system is a critical point in the evaluation of the transcriptional effects of bioactives.