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
Prep1 cDNA showed a 1.5- and 1.6-fold increase in eNOS
Thr495 and PKCα phosphorylation, respectively. Proinflammatory cytokines
Tnf-α and
Il-6 increased by 3.5 and 2.3-fold, respectively, in the presence of
Prep1, while the antioxidant genes
Sod2 and
Atf4 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
Thr495, PKCα phosphorylation, and proinflammatory cytokines and increased
Sod2 and
Atf4 mRNA levels. The experiments performed on the aorta of 18-month-old
Prep1 hypomorphic heterozygous mice (
Prep1i/+) expressing low levels of this protein showed a 54 and 60% decrease in PKCα and eNOS
Thr495 phosphorylation and a 45% reduction in
Tnf-α levels, with no change in
Il-6, compared to same-age WT mice. However, a significant decrease in
Sod2 and
Atf4 was observed in
Prep1i/+ old mice, indicating the lack of age-induced antioxidant response. These results suggest that
Prep1 deficiency partially improved the endothelial function in aged mice and suggested PREP1 as a novel target of resveratrol.
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