Resveratrol Improves Endothelial Function by A PREP1-Mediated Pathway in Mouse Aortic Endothelial Cells.

PREP1 is a homeodomain transcription factor that impairs metabolism and is involved in age-related aortic thickening. In this study, we evaluated the role of PREP1 on endothelial function. Mouse Aortic Endothelial Cells (MAECs) transiently transfected with a cDNA showed a 1.5- and 1.6-fold increase in eNOS and PKCα phosphorylation, respectively. Proinflammatory cytokines and increased by 3.5 and 2.3-fold, respectively, in the presence of , while the antioxidant genes and were significantly reduced. Bisindolylmaleimide reverted the effects induced by PREP1, suggesting PKCα to be a mediator of PREP1 action. Interestingly, resveratrol, a phenolic micronutrient compound, reduced the PREP1 levels, eNOS, PKCα phosphorylation, and proinflammatory cytokines and increased and mRNA levels. The experiments performed on the aorta of 18-month-old hypomorphic heterozygous mice () expressing low levels of this protein showed a 54 and 60% decrease in PKCα and eNOS phosphorylation and a 45% reduction in levels, with no change in , compared to same-age WT mice. However, a significant decrease in and was observed in old mice, indicating the lack of age-induced antioxidant response. These results suggest that deficiency partially improved the endothelial function in aged mice and suggested PREP1 as a novel target of resveratrol.