TMAO-Activated Hepatocyte-Derived Exosomes Are Widely Distributed in Mice with Different Patterns and Promote Vascular Inflammation
Background. Trimethylamine-N-oxide (TMAO) has been shown to be an important player in cardiovascular disease (CVD) by promoting vascular inflammation and endothelial dysfunction. We recently found that exosomes (Exos) released from TMAO-activated hepatocytes (TMAO-Exos) could significantly induce in...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
|
| Series: | Cardiology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2022/5166302 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832548646744227840 |
|---|---|
| author | Xiang Liu Jiazichao Tu Ziqin Zhou Bingxin Huang Jianrong Zhou Jimei Chen |
| author_facet | Xiang Liu Jiazichao Tu Ziqin Zhou Bingxin Huang Jianrong Zhou Jimei Chen |
| author_sort | Xiang Liu |
| collection | DOAJ |
| description | Background. Trimethylamine-N-oxide (TMAO) has been shown to be an important player in cardiovascular disease (CVD) by promoting vascular inflammation and endothelial dysfunction. We recently found that exosomes (Exos) released from TMAO-activated hepatocytes (TMAO-Exos) could significantly induce inflammation and endothelial dysfunction. However, understandings of how are the Exos secreted by hepatocytes, where are they distributed in vivo, and what effects will they have on vascular inflammation remain limited. The present study aimed to explore the hub genes involved in the production of TMAO-Exos and their distributions in vivo and effects on inflammation. Methods. The transcriptome profiles of primary rat hepatocytes stimulated with TMAO were obtained from the GSE135856 dataset in the Gene Expression Omnibus repository, and the hub genes associated with Exos were screened and verified by qPCR. Next, Exos derived from TMAO-treated hepatocytes were isolated using differential centrifugation and given intravenously to mice. After 24 h, the distributions of DiI-labelled Exos were visualized with a fluorescence microscope, and the levels of proinflammatory genes in the aorta were detected by qPCR. Results. Phgdh, Mdh2, Echs1, Rap2a, Gpd1l, and Slc3a2 were identified as hub genes that may be involved in the production of TMAO-Exos. And TMAO-Exos were found to be efficiently taken up by cardiomyocytes, hepatocytes, and endothelial cells in the aorta and gastrocnemius muscle. Furthermore, TMAO-Exos, but not control-Exos, could significantly promote the mRNA expressions of Tnf, Icam1, Sele, and Cox-2 in the aorta. Conclusions. We provided clues about how TMAO may stimulate hepatocytes to produce Exos and further offered evidence that Exos secreted by TMAO-treated hepatocytes could be widely distributed in vivo and promote vascular inflammation. |
| format | Article |
| id | doaj-art-ee4dbcdec9ca4ba7889b1280a0890891 |
| institution | Kabale University |
| issn | 2090-0597 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cardiology Research and Practice |
| spelling | doaj-art-ee4dbcdec9ca4ba7889b1280a08908912025-02-03T06:13:29ZengWileyCardiology Research and Practice2090-05972022-01-01202210.1155/2022/5166302TMAO-Activated Hepatocyte-Derived Exosomes Are Widely Distributed in Mice with Different Patterns and Promote Vascular InflammationXiang Liu0Jiazichao Tu1Ziqin Zhou2Bingxin Huang3Jianrong Zhou4Jimei Chen5Department of Cardiac SurgeryDepartment of Cardiac SurgeryDepartment of Cardiac SurgeryDepartment of Cardiac SurgeryDepartment of Cardiac SurgeryDepartment of Cardiac SurgeryBackground. Trimethylamine-N-oxide (TMAO) has been shown to be an important player in cardiovascular disease (CVD) by promoting vascular inflammation and endothelial dysfunction. We recently found that exosomes (Exos) released from TMAO-activated hepatocytes (TMAO-Exos) could significantly induce inflammation and endothelial dysfunction. However, understandings of how are the Exos secreted by hepatocytes, where are they distributed in vivo, and what effects will they have on vascular inflammation remain limited. The present study aimed to explore the hub genes involved in the production of TMAO-Exos and their distributions in vivo and effects on inflammation. Methods. The transcriptome profiles of primary rat hepatocytes stimulated with TMAO were obtained from the GSE135856 dataset in the Gene Expression Omnibus repository, and the hub genes associated with Exos were screened and verified by qPCR. Next, Exos derived from TMAO-treated hepatocytes were isolated using differential centrifugation and given intravenously to mice. After 24 h, the distributions of DiI-labelled Exos were visualized with a fluorescence microscope, and the levels of proinflammatory genes in the aorta were detected by qPCR. Results. Phgdh, Mdh2, Echs1, Rap2a, Gpd1l, and Slc3a2 were identified as hub genes that may be involved in the production of TMAO-Exos. And TMAO-Exos were found to be efficiently taken up by cardiomyocytes, hepatocytes, and endothelial cells in the aorta and gastrocnemius muscle. Furthermore, TMAO-Exos, but not control-Exos, could significantly promote the mRNA expressions of Tnf, Icam1, Sele, and Cox-2 in the aorta. Conclusions. We provided clues about how TMAO may stimulate hepatocytes to produce Exos and further offered evidence that Exos secreted by TMAO-treated hepatocytes could be widely distributed in vivo and promote vascular inflammation.http://dx.doi.org/10.1155/2022/5166302 |
| spellingShingle | Xiang Liu Jiazichao Tu Ziqin Zhou Bingxin Huang Jianrong Zhou Jimei Chen TMAO-Activated Hepatocyte-Derived Exosomes Are Widely Distributed in Mice with Different Patterns and Promote Vascular Inflammation Cardiology Research and Practice |
| title | TMAO-Activated Hepatocyte-Derived Exosomes Are Widely Distributed in Mice with Different Patterns and Promote Vascular Inflammation |
| title_full | TMAO-Activated Hepatocyte-Derived Exosomes Are Widely Distributed in Mice with Different Patterns and Promote Vascular Inflammation |
| title_fullStr | TMAO-Activated Hepatocyte-Derived Exosomes Are Widely Distributed in Mice with Different Patterns and Promote Vascular Inflammation |
| title_full_unstemmed | TMAO-Activated Hepatocyte-Derived Exosomes Are Widely Distributed in Mice with Different Patterns and Promote Vascular Inflammation |
| title_short | TMAO-Activated Hepatocyte-Derived Exosomes Are Widely Distributed in Mice with Different Patterns and Promote Vascular Inflammation |
| title_sort | tmao activated hepatocyte derived exosomes are widely distributed in mice with different patterns and promote vascular inflammation |
| url | http://dx.doi.org/10.1155/2022/5166302 |
| work_keys_str_mv | AT xiangliu tmaoactivatedhepatocytederivedexosomesarewidelydistributedinmicewithdifferentpatternsandpromotevascularinflammation AT jiazichaotu tmaoactivatedhepatocytederivedexosomesarewidelydistributedinmicewithdifferentpatternsandpromotevascularinflammation AT ziqinzhou tmaoactivatedhepatocytederivedexosomesarewidelydistributedinmicewithdifferentpatternsandpromotevascularinflammation AT bingxinhuang tmaoactivatedhepatocytederivedexosomesarewidelydistributedinmicewithdifferentpatternsandpromotevascularinflammation AT jianrongzhou tmaoactivatedhepatocytederivedexosomesarewidelydistributedinmicewithdifferentpatternsandpromotevascularinflammation AT jimeichen tmaoactivatedhepatocytederivedexosomesarewidelydistributedinmicewithdifferentpatternsandpromotevascularinflammation |