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Genome-Wide Transcriptional Profiling Reveals PHACTR1 as a Novel Molecular Target of Resveratrol in Endothelial Homeostasis
Atherosclerosis is a chronic inflammatory vascular disease in which endothelial cells play an important role in maintaining vascular homeostasis. Endotheliitis caused by endothelial dysfunction (ED) is the key cause for the development of cardiovascular and cerebrovascular diseases as well as other...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9658213/ https://www.ncbi.nlm.nih.gov/pubmed/36364780 http://dx.doi.org/10.3390/nu14214518 |
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author | Su, Meiming Zhao, Wenqi Li, Yujie Li, Hong Xu, Suowen Weng, Jianping |
author_facet | Su, Meiming Zhao, Wenqi Li, Yujie Li, Hong Xu, Suowen Weng, Jianping |
author_sort | Su, Meiming |
collection | PubMed |
description | Atherosclerosis is a chronic inflammatory vascular disease in which endothelial cells play an important role in maintaining vascular homeostasis. Endotheliitis caused by endothelial dysfunction (ED) is the key cause for the development of cardiovascular and cerebrovascular diseases as well as other vascular system diseases. Resveratrol (RES), a multi-functional polyphenol present in edible plants and fruits, prevents cardiovascular disease by regulating a variety of athero-relevant signaling pathways. By transcriptome profiling of RES-treated human umbilical vein endothelial cells (HUVECs) and in-depth bioinformatic analysis, we observed that differentially expressed genes (DEGs) were enriched in KEGG pathways of fluid shear stress and atherosclerosis, suggesting that the RES may serve as a good template for a shear stress mimetic drug that hold promise in combating atherosclerosis. A heat map and multiple datasets superimposed screening revealed that RES significantly down-regulated phosphatase and actin modulator 1 (PHACTR1), a pivotal coronary artery disease risk gene associated with endothelial inflammation and polyvascular diseases. We further demonstrate that RES down-regulated the gene and protein expression of PHACTR1 and inhibited TNF-α-induced adhesion of THP-1 monocytes to activated endothelial cells via suppressing the expression of PHACTR1. Taken together, our study reveals that PHACTR1 represents a new molecular target for RES to maintain endothelial cell homeostasis and prevent atherosclerotic cardiovascular disease. |
format | Online Article Text |
id | pubmed-9658213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96582132022-11-15 Genome-Wide Transcriptional Profiling Reveals PHACTR1 as a Novel Molecular Target of Resveratrol in Endothelial Homeostasis Su, Meiming Zhao, Wenqi Li, Yujie Li, Hong Xu, Suowen Weng, Jianping Nutrients Article Atherosclerosis is a chronic inflammatory vascular disease in which endothelial cells play an important role in maintaining vascular homeostasis. Endotheliitis caused by endothelial dysfunction (ED) is the key cause for the development of cardiovascular and cerebrovascular diseases as well as other vascular system diseases. Resveratrol (RES), a multi-functional polyphenol present in edible plants and fruits, prevents cardiovascular disease by regulating a variety of athero-relevant signaling pathways. By transcriptome profiling of RES-treated human umbilical vein endothelial cells (HUVECs) and in-depth bioinformatic analysis, we observed that differentially expressed genes (DEGs) were enriched in KEGG pathways of fluid shear stress and atherosclerosis, suggesting that the RES may serve as a good template for a shear stress mimetic drug that hold promise in combating atherosclerosis. A heat map and multiple datasets superimposed screening revealed that RES significantly down-regulated phosphatase and actin modulator 1 (PHACTR1), a pivotal coronary artery disease risk gene associated with endothelial inflammation and polyvascular diseases. We further demonstrate that RES down-regulated the gene and protein expression of PHACTR1 and inhibited TNF-α-induced adhesion of THP-1 monocytes to activated endothelial cells via suppressing the expression of PHACTR1. Taken together, our study reveals that PHACTR1 represents a new molecular target for RES to maintain endothelial cell homeostasis and prevent atherosclerotic cardiovascular disease. MDPI 2022-10-27 /pmc/articles/PMC9658213/ /pubmed/36364780 http://dx.doi.org/10.3390/nu14214518 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Su, Meiming Zhao, Wenqi Li, Yujie Li, Hong Xu, Suowen Weng, Jianping Genome-Wide Transcriptional Profiling Reveals PHACTR1 as a Novel Molecular Target of Resveratrol in Endothelial Homeostasis |
title | Genome-Wide Transcriptional Profiling Reveals PHACTR1 as a Novel Molecular Target of Resveratrol in Endothelial Homeostasis |
title_full | Genome-Wide Transcriptional Profiling Reveals PHACTR1 as a Novel Molecular Target of Resveratrol in Endothelial Homeostasis |
title_fullStr | Genome-Wide Transcriptional Profiling Reveals PHACTR1 as a Novel Molecular Target of Resveratrol in Endothelial Homeostasis |
title_full_unstemmed | Genome-Wide Transcriptional Profiling Reveals PHACTR1 as a Novel Molecular Target of Resveratrol in Endothelial Homeostasis |
title_short | Genome-Wide Transcriptional Profiling Reveals PHACTR1 as a Novel Molecular Target of Resveratrol in Endothelial Homeostasis |
title_sort | genome-wide transcriptional profiling reveals phactr1 as a novel molecular target of resveratrol in endothelial homeostasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9658213/ https://www.ncbi.nlm.nih.gov/pubmed/36364780 http://dx.doi.org/10.3390/nu14214518 |
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