Metabolic Syndrome Is Associated With Altered mRNA and miRNA Content in Human Circulating Extracellular Vesicles
As mediators of intercellular communication, circulating extracellular vehicles (EVs) can modulate tissue and cellular pathways by altering transcription profiles in recipient cells, and their content may reflect the status of their parent cells. However, whether their cargo is altered in the metabo...
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.687586/full |
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| author | Yongxin Li Yongxin Li Yu Meng Yu Meng Xiangyang Zhu Andre Van Wijnen Alfonso Eirin Lilach O. Lerman |
| author_facet | Yongxin Li Yongxin Li Yu Meng Yu Meng Xiangyang Zhu Andre Van Wijnen Alfonso Eirin Lilach O. Lerman |
| author_sort | Yongxin Li |
| collection | DOAJ |
| description | As mediators of intercellular communication, circulating extracellular vehicles (EVs) can modulate tissue and cellular pathways by altering transcription profiles in recipient cells, and their content may reflect the status of their parent cells. However, whether their cargo is altered in the metabolic syndrome (Mets) remains unclear. We hypothesized that MetS altered mRNAs and miRNAs packed within circulating-EVs. EVs were collected from plasma of patients with MetS or age-matched Lean controls (n=4 each). RNA sequencing was performed to identify dysregulated mRNAs and miRNAs, and analyze genes targeted by miRNAs, top pathways, and diseases associated with MetS-EVs. MetS patients showed elevated body weight, blood pressure, glucose, insulin, and liver injury markers levels. 1,446 mRNAs were downregulated and 32 upregulated in MetS- compared to Lean-EVs, whereas 40 miRNAs were selectively enriched and 10 downregulated in MetS-EVs. MetS upregulated in EVs genes involved in apoptosis, mitochondrial regulation, transport, and lipoproteins, but downregulated vessel and heart development, protein complex biogenesis, and angiogenesis. MetS also upregulated miRNAs targeting genes implicated in cellular processes, including oxidation–reduction, and downregulated miRNAs capable of modulating catalytic activity, as well as heart, blood vessel, and skeletal development, transcriptional regulation, apoptosis, and cell cycle. Our study, thus, indicates that human subjects with MetS show modified cargo of circulating EVs, which in turn may modulate several critical cellular functions and fate. These EVs may reflect the anomalous status of their parent cells, and potentially serve as important regulators, biomarkers, and targets in the progression and treatment of MetS. |
| first_indexed | 2024-12-17T22:39:25Z |
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| id | doaj.art-2b4d8dbbacb5418fb36265aad45d42a8 |
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| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-17T22:39:25Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-2b4d8dbbacb5418fb36265aad45d42a82022-12-21T21:30:00ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-08-011210.3389/fendo.2021.687586687586Metabolic Syndrome Is Associated With Altered mRNA and miRNA Content in Human Circulating Extracellular VesiclesYongxin Li0Yongxin Li1Yu Meng2Yu Meng3Xiangyang Zhu4Andre Van Wijnen5Alfonso Eirin6Lilach O. Lerman7Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United StatesCentral Laboratory, The Fifth Affiliated Hospital of Jinan University, Heyuan, ChinaDepartment of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United StatesDepartments of Orthopedic Surgery, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, United StatesDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United StatesDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United StatesAs mediators of intercellular communication, circulating extracellular vehicles (EVs) can modulate tissue and cellular pathways by altering transcription profiles in recipient cells, and their content may reflect the status of their parent cells. However, whether their cargo is altered in the metabolic syndrome (Mets) remains unclear. We hypothesized that MetS altered mRNAs and miRNAs packed within circulating-EVs. EVs were collected from plasma of patients with MetS or age-matched Lean controls (n=4 each). RNA sequencing was performed to identify dysregulated mRNAs and miRNAs, and analyze genes targeted by miRNAs, top pathways, and diseases associated with MetS-EVs. MetS patients showed elevated body weight, blood pressure, glucose, insulin, and liver injury markers levels. 1,446 mRNAs were downregulated and 32 upregulated in MetS- compared to Lean-EVs, whereas 40 miRNAs were selectively enriched and 10 downregulated in MetS-EVs. MetS upregulated in EVs genes involved in apoptosis, mitochondrial regulation, transport, and lipoproteins, but downregulated vessel and heart development, protein complex biogenesis, and angiogenesis. MetS also upregulated miRNAs targeting genes implicated in cellular processes, including oxidation–reduction, and downregulated miRNAs capable of modulating catalytic activity, as well as heart, blood vessel, and skeletal development, transcriptional regulation, apoptosis, and cell cycle. Our study, thus, indicates that human subjects with MetS show modified cargo of circulating EVs, which in turn may modulate several critical cellular functions and fate. These EVs may reflect the anomalous status of their parent cells, and potentially serve as important regulators, biomarkers, and targets in the progression and treatment of MetS.https://www.frontiersin.org/articles/10.3389/fendo.2021.687586/fullmetabolic syndromeRNA sequencingcirculationextracellular vesiclesextracellular vehicles |
| spellingShingle | Yongxin Li Yongxin Li Yu Meng Yu Meng Xiangyang Zhu Andre Van Wijnen Alfonso Eirin Lilach O. Lerman Metabolic Syndrome Is Associated With Altered mRNA and miRNA Content in Human Circulating Extracellular Vesicles Frontiers in Endocrinology metabolic syndrome RNA sequencing circulation extracellular vesicles extracellular vehicles |
| title | Metabolic Syndrome Is Associated With Altered mRNA and miRNA Content in Human Circulating Extracellular Vesicles |
| title_full | Metabolic Syndrome Is Associated With Altered mRNA and miRNA Content in Human Circulating Extracellular Vesicles |
| title_fullStr | Metabolic Syndrome Is Associated With Altered mRNA and miRNA Content in Human Circulating Extracellular Vesicles |
| title_full_unstemmed | Metabolic Syndrome Is Associated With Altered mRNA and miRNA Content in Human Circulating Extracellular Vesicles |
| title_short | Metabolic Syndrome Is Associated With Altered mRNA and miRNA Content in Human Circulating Extracellular Vesicles |
| title_sort | metabolic syndrome is associated with altered mrna and mirna content in human circulating extracellular vesicles |
| topic | metabolic syndrome RNA sequencing circulation extracellular vesicles extracellular vehicles |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.687586/full |
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