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Resveratrol Improves Endothelial Function by A PREP1-Mediated Pathway in Mouse Aortic Endothelial Cells
Serena Cabaro1, Ayewa L Agognon1, Cecilia Nigro1
1Department of Translational Medicine, Federico II University of Naples and URT Genomic of Diabetes of Institute of Experimental Endocrinology and Oncology, National Council of Research (CNR), Via Pansini 5, 80131 Naples, Italy.
International Journal of Molecular Sciences
|August 12, 2023
Summary
The transcription factor PREP1 impairs endothelial function by increasing inflammation and reducing antioxidant genes. PREP1 deficiency partially improved aged mouse endothelial function, suggesting it as a resveratrol target.
Area of Science:
- Molecular Biology
- Cardiovascular Biology
- Aging Research
Background:
- PREP1 (Prophet of PITX2) is a homeodomain transcription factor implicated in metabolic dysfunction and age-related aortic thickening.
- Endothelial dysfunction is a key factor in cardiovascular disease and aging.
Purpose of the Study:
- To investigate the role of PREP1 in endothelial function and its modulation by resveratrol.
- To explore the impact of PREP1 deficiency on endothelial function in aged mice.
Main Methods:
- In vitro studies using Mouse Aortic Endothelial Cells (MAECs) transfected with PREP1.
- In vivo studies using 18-month-old Prep1 hypomorphic heterozygous mice and wild-type (WT) littermates.
- Analysis of eNOS, PKCα phosphorylation, inflammatory cytokines (Tnf-α, Il-6), and antioxidant genes (Sod2, Atf4).
Main Results:
- Overexpression of PREP1 in MAECs increased eNOS and PKCα phosphorylation, upregulated proinflammatory cytokines, and reduced antioxidant gene expression.
- Bisindolylmaleimide treatment reversed PREP1-induced effects, indicating PKCα mediation.
- Resveratrol decreased PREP1 levels and its downstream effects, while increasing antioxidant gene expression.
- Prep1 deficient aged mice showed reduced PKCα and eNOS phosphorylation and lower Tnf-α levels, but impaired antioxidant response.
Conclusions:
- PREP1 negatively regulates endothelial function, partly through PKCα signaling and modulation of inflammatory and antioxidant pathways.
- Partial PREP1 deficiency offers some protection against age-related endothelial dysfunction in mice.
- PREP1 emerges as a potential therapeutic target for resveratrol in improving endothelial health.
