Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis
Hydroxytyrosol (HT), a peculiar olive and olive oil phenolic antioxidant, plays a significant role in the endothelial and cardiovascular protection associated with olive oil consumption. However, studies examining the effects of HT on the whole-genome expression of endothelial cells, which are promi...
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oai:doaj.org-article:42d7c5b67ef44102a42ca2b15832eeb62021-11-25T18:35:51ZNutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis10.3390/nu131139902072-6643https://doaj.org/article/42d7c5b67ef44102a42ca2b15832eeb62021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/3990https://doaj.org/toc/2072-6643Hydroxytyrosol (HT), a peculiar olive and olive oil phenolic antioxidant, plays a significant role in the endothelial and cardiovascular protection associated with olive oil consumption. However, studies examining the effects of HT on the whole-genome expression of endothelial cells, which are prominent targets for vasculo-protective effects of olive oil polyphenols, have been lacking. This study aims to comprehensively evaluate the genomic effects exerted by HT, at the transcriptional level, in endothelial cells under resting or proinflammatory conditions. Human umbilical vein endothelial cells (HUVECs) were treated with 10 µmol/L HT for 1 h and then stimulated with 5 ng/mL interleukin (IL)-1β for 3 h. Total RNA was extracted, and gene expression profile assessed with microarray analysis. Functional enrichment analysis and pathway analysis were performed by Ingenuity Pathways Analysis. Microarray data were validated by qRT-PCR. Fixing a significance threshold at 1.5-fold change, HT affected the expression of 708 and 599 genes, respectively, in HUVECs under resting and IL-1β-stimulated conditions; among these, 190 were common to both conditions. Unfolded protein response (UPR) and endoplasmic reticulum stress resulted from the two top canonical pathways common between HT and HT-IL-1β affected genes. IL-17F/A signaling was found in the top canonical pathways of HT modified genes under resting unstimulated conditions, whereas cardiac hypertrophy signaling was identified among the pathways affected by HT-IL-1β. The transcriptomic analysis allowed pinpointing immunological, inflammatory, proliferative, and metabolic-related pathways as the most affected by HT in endothelial cells. It also revealed previously unsuspected genes and related gene pathways affected by HT, thus broadening our knowledge of its biological properties. The unbiased identification of novel genes regulated by HT improves our understanding of mechanisms by which olive oil prevents or attenuates inflammatory diseases and identifies new genes to be enquired as potential contributors to the inter-individual variation in response to functional food consumption.Maria Annunziata CarluccioRosanna MartinelliMarika MassaroNadia CalabrisoEgeria ScodittiMichele MaffiaTiziano VerriValentina GattaRaffaele De CaterinaMDPI AGarticlehydroxytyrosolnutrigenomicsgene expressiontranscriptomicsmicroarray analysisendothelial cellsNutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 3990, p 3990 (2021) |
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hydroxytyrosol nutrigenomics gene expression transcriptomics microarray analysis endothelial cells Nutrition. Foods and food supply TX341-641 |
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hydroxytyrosol nutrigenomics gene expression transcriptomics microarray analysis endothelial cells Nutrition. Foods and food supply TX341-641 Maria Annunziata Carluccio Rosanna Martinelli Marika Massaro Nadia Calabriso Egeria Scoditti Michele Maffia Tiziano Verri Valentina Gatta Raffaele De Caterina Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis |
description |
Hydroxytyrosol (HT), a peculiar olive and olive oil phenolic antioxidant, plays a significant role in the endothelial and cardiovascular protection associated with olive oil consumption. However, studies examining the effects of HT on the whole-genome expression of endothelial cells, which are prominent targets for vasculo-protective effects of olive oil polyphenols, have been lacking. This study aims to comprehensively evaluate the genomic effects exerted by HT, at the transcriptional level, in endothelial cells under resting or proinflammatory conditions. Human umbilical vein endothelial cells (HUVECs) were treated with 10 µmol/L HT for 1 h and then stimulated with 5 ng/mL interleukin (IL)-1β for 3 h. Total RNA was extracted, and gene expression profile assessed with microarray analysis. Functional enrichment analysis and pathway analysis were performed by Ingenuity Pathways Analysis. Microarray data were validated by qRT-PCR. Fixing a significance threshold at 1.5-fold change, HT affected the expression of 708 and 599 genes, respectively, in HUVECs under resting and IL-1β-stimulated conditions; among these, 190 were common to both conditions. Unfolded protein response (UPR) and endoplasmic reticulum stress resulted from the two top canonical pathways common between HT and HT-IL-1β affected genes. IL-17F/A signaling was found in the top canonical pathways of HT modified genes under resting unstimulated conditions, whereas cardiac hypertrophy signaling was identified among the pathways affected by HT-IL-1β. The transcriptomic analysis allowed pinpointing immunological, inflammatory, proliferative, and metabolic-related pathways as the most affected by HT in endothelial cells. It also revealed previously unsuspected genes and related gene pathways affected by HT, thus broadening our knowledge of its biological properties. The unbiased identification of novel genes regulated by HT improves our understanding of mechanisms by which olive oil prevents or attenuates inflammatory diseases and identifies new genes to be enquired as potential contributors to the inter-individual variation in response to functional food consumption. |
format |
article |
author |
Maria Annunziata Carluccio Rosanna Martinelli Marika Massaro Nadia Calabriso Egeria Scoditti Michele Maffia Tiziano Verri Valentina Gatta Raffaele De Caterina |
author_facet |
Maria Annunziata Carluccio Rosanna Martinelli Marika Massaro Nadia Calabriso Egeria Scoditti Michele Maffia Tiziano Verri Valentina Gatta Raffaele De Caterina |
author_sort |
Maria Annunziata Carluccio |
title |
Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis |
title_short |
Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis |
title_full |
Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis |
title_fullStr |
Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis |
title_full_unstemmed |
Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis |
title_sort |
nutrigenomic effect of hydroxytyrosol in vascular endothelial cells: a transcriptomic profile analysis |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doaj.org/article/42d7c5b67ef44102a42ca2b15832eeb6 |
work_keys_str_mv |
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