Fluid Shear Stress Regulates the Landscape of microRNAs in Endothelial Cell-Derived Small Extracellular Vesicles and Modulates the Function of Endothelial Cells
Blood fluid shear stress (FSS) modulates endothelial function and vascular pathophysiology. The small extracellular vesicles (sEVs) such as exosomes are potent mediators of intercellular communication, and their contents reflect cellular stress. Here, we explored the miRNA profiles in endothelial ce...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/3/1314 |
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| author | Jihwa Chung Kyoung Hwa Kim Namhee Yu Shung Hyun An Sanghyuk Lee Kihwan Kwon |
| author_facet | Jihwa Chung Kyoung Hwa Kim Namhee Yu Shung Hyun An Sanghyuk Lee Kihwan Kwon |
| author_sort | Jihwa Chung |
| collection | DOAJ |
| description | Blood fluid shear stress (FSS) modulates endothelial function and vascular pathophysiology. The small extracellular vesicles (sEVs) such as exosomes are potent mediators of intercellular communication, and their contents reflect cellular stress. Here, we explored the miRNA profiles in endothelial cells (EC)-derived sEVs (EC-sEVs) under atheroprotective laminar shear stress (LSS) and atheroprone low-oscillatory shear stress (OSS) and conducted a network analysis to identify the main biological processes modulated by sEVs’ miRNAs. The EC-sEVs were collected from culture media of human umbilical vein endothelial cells exposed to atheroprotective LSS (20 dyne/cm<sup>2</sup>) and atheroprone OSS (±5 dyne/cm<sup>2</sup>). We explored the miRNA profiles in FSS-induced EC-sEVs (LSS-sEVs and OSS-sEVs) and conducted a network analysis to identify the main biological processes modulated by sEVs’ miRNAs. In vivo studies were performed in a mouse model of partial carotid ligation. The sEVs’ miRNAs-targeted genes were enriched for endothelial activation such as angiogenesis, cell migration, and vascular inflammation. OSS-sEVs promoted tube formation, cell migration, monocyte adhesion, and apoptosis, and upregulated the expression of proteins that stimulate these biological processes. FSS-induced EC-sEVs had the same effects on endothelial mechanotransduction signaling as direct stimulation by FSS. In vivo studies showed that LSS-sEVs reduced the expression of pro-inflammatory genes, whereas OSS-sEVs had the opposite effect. Understanding the landscape of EC-exosomal miRNAs regulated by differential FSS patterns, this research establishes their biological functions on a system level and provides a platform for modulating the overall phenotypic effects of sEVs. |
| first_indexed | 2024-03-09T23:48:22Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:48:22Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-13cfffa71f6143cd9fe610dede4b66b92023-11-23T16:38:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01233131410.3390/ijms23031314Fluid Shear Stress Regulates the Landscape of microRNAs in Endothelial Cell-Derived Small Extracellular Vesicles and Modulates the Function of Endothelial CellsJihwa Chung0Kyoung Hwa Kim1Namhee Yu2Shung Hyun An3Sanghyuk Lee4Kihwan Kwon5Exollence Biotechnology Co., Ltd., Seoul 07985, KoreaExollence Biotechnology Co., Ltd., Seoul 07985, KoreaResearch Institute, National Cancer Center, Goyangsi 10408, KoreaExollence Biotechnology Co., Ltd., Seoul 07985, KoreaDepartment of Life Sciences, Ewha Womans University, Seoul 03760, KoreaExollence Biotechnology Co., Ltd., Seoul 07985, KoreaBlood fluid shear stress (FSS) modulates endothelial function and vascular pathophysiology. The small extracellular vesicles (sEVs) such as exosomes are potent mediators of intercellular communication, and their contents reflect cellular stress. Here, we explored the miRNA profiles in endothelial cells (EC)-derived sEVs (EC-sEVs) under atheroprotective laminar shear stress (LSS) and atheroprone low-oscillatory shear stress (OSS) and conducted a network analysis to identify the main biological processes modulated by sEVs’ miRNAs. The EC-sEVs were collected from culture media of human umbilical vein endothelial cells exposed to atheroprotective LSS (20 dyne/cm<sup>2</sup>) and atheroprone OSS (±5 dyne/cm<sup>2</sup>). We explored the miRNA profiles in FSS-induced EC-sEVs (LSS-sEVs and OSS-sEVs) and conducted a network analysis to identify the main biological processes modulated by sEVs’ miRNAs. In vivo studies were performed in a mouse model of partial carotid ligation. The sEVs’ miRNAs-targeted genes were enriched for endothelial activation such as angiogenesis, cell migration, and vascular inflammation. OSS-sEVs promoted tube formation, cell migration, monocyte adhesion, and apoptosis, and upregulated the expression of proteins that stimulate these biological processes. FSS-induced EC-sEVs had the same effects on endothelial mechanotransduction signaling as direct stimulation by FSS. In vivo studies showed that LSS-sEVs reduced the expression of pro-inflammatory genes, whereas OSS-sEVs had the opposite effect. Understanding the landscape of EC-exosomal miRNAs regulated by differential FSS patterns, this research establishes their biological functions on a system level and provides a platform for modulating the overall phenotypic effects of sEVs.https://www.mdpi.com/1422-0067/23/3/1314shear stressendothelial cellsmall extracellular vesiclesmicroRNAsystemic network analyses |
| spellingShingle | Jihwa Chung Kyoung Hwa Kim Namhee Yu Shung Hyun An Sanghyuk Lee Kihwan Kwon Fluid Shear Stress Regulates the Landscape of microRNAs in Endothelial Cell-Derived Small Extracellular Vesicles and Modulates the Function of Endothelial Cells International Journal of Molecular Sciences shear stress endothelial cell small extracellular vesicles microRNA systemic network analyses |
| title | Fluid Shear Stress Regulates the Landscape of microRNAs in Endothelial Cell-Derived Small Extracellular Vesicles and Modulates the Function of Endothelial Cells |
| title_full | Fluid Shear Stress Regulates the Landscape of microRNAs in Endothelial Cell-Derived Small Extracellular Vesicles and Modulates the Function of Endothelial Cells |
| title_fullStr | Fluid Shear Stress Regulates the Landscape of microRNAs in Endothelial Cell-Derived Small Extracellular Vesicles and Modulates the Function of Endothelial Cells |
| title_full_unstemmed | Fluid Shear Stress Regulates the Landscape of microRNAs in Endothelial Cell-Derived Small Extracellular Vesicles and Modulates the Function of Endothelial Cells |
| title_short | Fluid Shear Stress Regulates the Landscape of microRNAs in Endothelial Cell-Derived Small Extracellular Vesicles and Modulates the Function of Endothelial Cells |
| title_sort | fluid shear stress regulates the landscape of micrornas in endothelial cell derived small extracellular vesicles and modulates the function of endothelial cells |
| topic | shear stress endothelial cell small extracellular vesicles microRNA systemic network analyses |
| url | https://www.mdpi.com/1422-0067/23/3/1314 |
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