{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:21:51Z","timestamp":1760149311998,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T00:00:00Z","timestamp":1690243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Campania"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 eNOSThr495 and PKC\u03b1 phosphorylation, respectively. Proinflammatory cytokines Tnf-\u03b1 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 PKC\u03b1 to be a mediator of PREP1 action. Interestingly, resveratrol, a phenolic micronutrient compound, reduced the PREP1 levels, eNOSThr495, PKC\u03b1 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 PKC\u03b1 and eNOSThr495 phosphorylation and a 45% reduction in Tnf-\u03b1 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.<\/jats:p>","DOI":"10.3390\/ijms241511891","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:45:02Z","timestamp":1690332302000},"page":"11891","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Resveratrol Improves Endothelial Function by A PREP1-Mediated Pathway in Mouse Aortic Endothelial Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9946-4475","authenticated-orcid":false,"given":"Serena","family":"Cabaro","sequence":"first","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayewa L.","family":"Agognon","sequence":"additional","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8924-9731","authenticated-orcid":false,"given":"Cecilia","family":"Nigro","sequence":"additional","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Orso","sequence":"additional","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Immacolata","family":"Prevenzano","sequence":"additional","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0193-6826","authenticated-orcid":false,"given":"Alessia","family":"Leone","sequence":"additional","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Morelli","sequence":"additional","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Mormone","sequence":"additional","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Romano","sequence":"additional","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Miele","sequence":"additional","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Beguinot","sequence":"additional","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7020-6870","authenticated-orcid":false,"given":"Pietro","family":"Formisano","sequence":"additional","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4375-4526","authenticated-orcid":false,"given":"Francesco","family":"Oriente","sequence":"additional","affiliation":[{"name":"Department 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"},{"name":"Center for Basic and Clinical Immunology Research (CISI), University of Naples 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