Docosahexaenoic Acid Alleviates Trimethylamine-<i>N</i>-oxide-mediated Impairment of Neovascularization in Human Endothelial Progenitor Cells
Background: Human endothelial progenitor cells (hEPCs), originating from hemangioblasts in bone marrow (BM), migrate into the blood circulation, differentiate into endothelial cells, and could act as an alternative tool for tissue regeneration. In addition, trimethylamine-<i>N</i>-oxide...
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MDPI AG
2023-05-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/9/2190 |
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| author | Jia-Ning Syu Hung-Yu Lin Tun Yu Huang Der-Yen Lee En-Pei Isabel Chiang Feng-Yao Tang |
| author_facet | Jia-Ning Syu Hung-Yu Lin Tun Yu Huang Der-Yen Lee En-Pei Isabel Chiang Feng-Yao Tang |
| author_sort | Jia-Ning Syu |
| collection | DOAJ |
| description | Background: Human endothelial progenitor cells (hEPCs), originating from hemangioblasts in bone marrow (BM), migrate into the blood circulation, differentiate into endothelial cells, and could act as an alternative tool for tissue regeneration. In addition, trimethylamine-<i>N</i>-oxide (TMAO), one of the gut microbiota metabolites, has been identified as an atherosclerosis risk factor. However, the deleterious effects of TMAO on the neovascularization of hEPCs have not been studied yet. Results: Our results demonstrated that TMAO dose-dependently impaired human stem cell factor (SCF)-mediated neovascularization in hEPCs. The action of TMAO was through the inactivation of Akt/endothelial nitric oxide synthase (eNOS), MAPK/ERK signaling pathways, and an upregulation of microRNA (miR)-221. Docosahexaenoic acid (DHA) could effectively inhibit the cellular miR-221 level and induce the phosphorylation level of Akt/eNOS, MAPK/ERK signaling molecules, and neovascularization in hEPCs. DHA enhanced cellular amounts of reduced form glutathione (GSH) through an increased expression of the gamma-glutamylcysteine synthetase (γ-GCS) protein. Conclusions: TMAO could significantly inhibit SCF-mediated neovascularization, in part in association with an upregulation of miR-221 level, inactivation of Akt/eNOS and MAPK/ERK cascades, suppression of γ-GCS protein, and decreased levels of GSH and GSH/GSSG ratio. Furthermore, the DHA could alleviate the detrimental effects of TMAO and induce neovasculogenesis through suppression of miR-221 level, activation of Akt/eNOS and MAPK/ERK signaling cascades, increased expression of γ-GCS protein, and increment of cellular GSH level and GSH/GSSG ratio in hEPCs. |
| first_indexed | 2024-03-11T04:10:02Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T04:10:02Z |
| publishDate | 2023-05-01 |
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| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-5dce07730c114f64ab7082d122e1471f2023-11-17T23:30:22ZengMDPI AGNutrients2072-66432023-05-01159219010.3390/nu15092190Docosahexaenoic Acid Alleviates Trimethylamine-<i>N</i>-oxide-mediated Impairment of Neovascularization in Human Endothelial Progenitor CellsJia-Ning Syu0Hung-Yu Lin1Tun Yu Huang2Der-Yen Lee3En-Pei Isabel Chiang4Feng-Yao Tang5Biomedical Science Laboratory, Department of Nutrition, China Medical University, Taichung 40604, TaiwanResearch Assistant Center, Show Chwan Memorial Hospital, Changhua 500, TaiwanProspective Wound Medicine Research Center, Show Chwan Memorial Hospital, Changhua 500, TaiwanGraduate Institute of Integrated Medicine, China Medical University, Taichung 40604, TaiwanDepartment of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, TaiwanBiomedical Science Laboratory, Department of Nutrition, China Medical University, Taichung 40604, TaiwanBackground: Human endothelial progenitor cells (hEPCs), originating from hemangioblasts in bone marrow (BM), migrate into the blood circulation, differentiate into endothelial cells, and could act as an alternative tool for tissue regeneration. In addition, trimethylamine-<i>N</i>-oxide (TMAO), one of the gut microbiota metabolites, has been identified as an atherosclerosis risk factor. However, the deleterious effects of TMAO on the neovascularization of hEPCs have not been studied yet. Results: Our results demonstrated that TMAO dose-dependently impaired human stem cell factor (SCF)-mediated neovascularization in hEPCs. The action of TMAO was through the inactivation of Akt/endothelial nitric oxide synthase (eNOS), MAPK/ERK signaling pathways, and an upregulation of microRNA (miR)-221. Docosahexaenoic acid (DHA) could effectively inhibit the cellular miR-221 level and induce the phosphorylation level of Akt/eNOS, MAPK/ERK signaling molecules, and neovascularization in hEPCs. DHA enhanced cellular amounts of reduced form glutathione (GSH) through an increased expression of the gamma-glutamylcysteine synthetase (γ-GCS) protein. Conclusions: TMAO could significantly inhibit SCF-mediated neovascularization, in part in association with an upregulation of miR-221 level, inactivation of Akt/eNOS and MAPK/ERK cascades, suppression of γ-GCS protein, and decreased levels of GSH and GSH/GSSG ratio. Furthermore, the DHA could alleviate the detrimental effects of TMAO and induce neovasculogenesis through suppression of miR-221 level, activation of Akt/eNOS and MAPK/ERK signaling cascades, increased expression of γ-GCS protein, and increment of cellular GSH level and GSH/GSSG ratio in hEPCs.https://www.mdpi.com/2072-6643/15/9/2190trimethylamine-<i>N</i>-oxidedocosahexaenoic acidendothelial nitric oxide synthasemicroRNA 221glutathioneendothelial progenitor cells |
| spellingShingle | Jia-Ning Syu Hung-Yu Lin Tun Yu Huang Der-Yen Lee En-Pei Isabel Chiang Feng-Yao Tang Docosahexaenoic Acid Alleviates Trimethylamine-<i>N</i>-oxide-mediated Impairment of Neovascularization in Human Endothelial Progenitor Cells Nutrients trimethylamine-<i>N</i>-oxide docosahexaenoic acid endothelial nitric oxide synthase microRNA 221 glutathione endothelial progenitor cells |
| title | Docosahexaenoic Acid Alleviates Trimethylamine-<i>N</i>-oxide-mediated Impairment of Neovascularization in Human Endothelial Progenitor Cells |
| title_full | Docosahexaenoic Acid Alleviates Trimethylamine-<i>N</i>-oxide-mediated Impairment of Neovascularization in Human Endothelial Progenitor Cells |
| title_fullStr | Docosahexaenoic Acid Alleviates Trimethylamine-<i>N</i>-oxide-mediated Impairment of Neovascularization in Human Endothelial Progenitor Cells |
| title_full_unstemmed | Docosahexaenoic Acid Alleviates Trimethylamine-<i>N</i>-oxide-mediated Impairment of Neovascularization in Human Endothelial Progenitor Cells |
| title_short | Docosahexaenoic Acid Alleviates Trimethylamine-<i>N</i>-oxide-mediated Impairment of Neovascularization in Human Endothelial Progenitor Cells |
| title_sort | docosahexaenoic acid alleviates trimethylamine i n i oxide mediated impairment of neovascularization in human endothelial progenitor cells |
| topic | trimethylamine-<i>N</i>-oxide docosahexaenoic acid endothelial nitric oxide synthase microRNA 221 glutathione endothelial progenitor cells |
| url | https://www.mdpi.com/2072-6643/15/9/2190 |
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