Role of triggering receptor expressed on myeloid cells-1 in the mechanotransduction signaling pathways that link low shear stress with inflammation
Abstract This study sought to investigate the role of triggering receptor expressed on myeloid cells-1 (TREM-1) in the mechanotransduction signaling pathways that link low shear stress with inflammation. Human coronary artery endothelial cells, human coronary artery smooth muscle cells, and THP-1 mo...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-31763-w |
| _version_ | 1797865114936803328 |
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| author | Martin Liu Anastasios Nikolaos Panagopoulos Usama M. Oguz Saurabhi Samant Charu Hasini Vasa Devendra K. Agrawal Yiannis S. Chatzizisis |
| author_facet | Martin Liu Anastasios Nikolaos Panagopoulos Usama M. Oguz Saurabhi Samant Charu Hasini Vasa Devendra K. Agrawal Yiannis S. Chatzizisis |
| author_sort | Martin Liu |
| collection | DOAJ |
| description | Abstract This study sought to investigate the role of triggering receptor expressed on myeloid cells-1 (TREM-1) in the mechanotransduction signaling pathways that link low shear stress with inflammation. Human coronary artery endothelial cells, human coronary artery smooth muscle cells, and THP-1 monocytes were co-cultured and exposed to varying endothelial shear stress (ESS) conditions: low (5 ± 3 dynes/cm2), medium (10 ± 3 dynes/cm2), and high (15 ± 3 dynes/cm2). We showed that low ESS increased the expression of TREM-1 by the cultured cells leading to increased production of inflammatory mediators and matrix-degrading enzymes, whereas high ESS did not have a significant effect in the expression of TREM-1 and inflammatory mediators. Furthermore, TREM-1 transcriptional inhibition with siRNA in endothelial cells, smooth muscle cells, and monocytes exposed to low ESS, led to a significant reduction in the production of vascular inflammatory mediators and matrix-degrading enzymes. Additionally, we identified the transcription factors that appear to upregulate the TREM-1 gene expression in response to low ESS. To the best of our knowledge, this is the first study to investigate the pathophysiologic association and molecular pathways that link low ESS, TREM-1, and inflammation using a sophisticated in-vitro model of atherosclerosis. Future studies on animals and humans are warranted to investigate the potential of TREM-1 inhibitors as adjunctive anti-atherosclerotic therapies. |
| first_indexed | 2024-04-09T23:02:46Z |
| format | Article |
| id | doaj.art-5172b6d683df480bb888c77a1b3a127b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T23:02:46Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5172b6d683df480bb888c77a1b3a127b2023-03-22T10:52:46ZengNature PortfolioScientific Reports2045-23222023-03-0113111110.1038/s41598-023-31763-wRole of triggering receptor expressed on myeloid cells-1 in the mechanotransduction signaling pathways that link low shear stress with inflammationMartin Liu0Anastasios Nikolaos Panagopoulos1Usama M. Oguz2Saurabhi Samant3Charu Hasini Vasa4Devendra K. Agrawal5Yiannis S. Chatzizisis6Computational Cardiovascular Simulations Center, Division of Cardiovascular Medicine, Miller School of Medicine, University of MiamiCardiovascular Biology and Biomechanics Laboratory, Cardiovascular Division, Department of Internal Medicine, University of Nebraska Medical CenterComputational Cardiovascular Simulations Center, Division of Cardiovascular Medicine, Miller School of Medicine, University of MiamiCardiovascular Biology and Biomechanics Laboratory, Cardiovascular Division, Department of Internal Medicine, University of Nebraska Medical CenterComputational Cardiovascular Simulations Center, Division of Cardiovascular Medicine, Miller School of Medicine, University of MiamiDepartment of Translational Research, Western University of Health ScienceComputational Cardiovascular Simulations Center, Division of Cardiovascular Medicine, Miller School of Medicine, University of MiamiAbstract This study sought to investigate the role of triggering receptor expressed on myeloid cells-1 (TREM-1) in the mechanotransduction signaling pathways that link low shear stress with inflammation. Human coronary artery endothelial cells, human coronary artery smooth muscle cells, and THP-1 monocytes were co-cultured and exposed to varying endothelial shear stress (ESS) conditions: low (5 ± 3 dynes/cm2), medium (10 ± 3 dynes/cm2), and high (15 ± 3 dynes/cm2). We showed that low ESS increased the expression of TREM-1 by the cultured cells leading to increased production of inflammatory mediators and matrix-degrading enzymes, whereas high ESS did not have a significant effect in the expression of TREM-1 and inflammatory mediators. Furthermore, TREM-1 transcriptional inhibition with siRNA in endothelial cells, smooth muscle cells, and monocytes exposed to low ESS, led to a significant reduction in the production of vascular inflammatory mediators and matrix-degrading enzymes. Additionally, we identified the transcription factors that appear to upregulate the TREM-1 gene expression in response to low ESS. To the best of our knowledge, this is the first study to investigate the pathophysiologic association and molecular pathways that link low ESS, TREM-1, and inflammation using a sophisticated in-vitro model of atherosclerosis. Future studies on animals and humans are warranted to investigate the potential of TREM-1 inhibitors as adjunctive anti-atherosclerotic therapies.https://doi.org/10.1038/s41598-023-31763-w |
| spellingShingle | Martin Liu Anastasios Nikolaos Panagopoulos Usama M. Oguz Saurabhi Samant Charu Hasini Vasa Devendra K. Agrawal Yiannis S. Chatzizisis Role of triggering receptor expressed on myeloid cells-1 in the mechanotransduction signaling pathways that link low shear stress with inflammation Scientific Reports |
| title | Role of triggering receptor expressed on myeloid cells-1 in the mechanotransduction signaling pathways that link low shear stress with inflammation |
| title_full | Role of triggering receptor expressed on myeloid cells-1 in the mechanotransduction signaling pathways that link low shear stress with inflammation |
| title_fullStr | Role of triggering receptor expressed on myeloid cells-1 in the mechanotransduction signaling pathways that link low shear stress with inflammation |
| title_full_unstemmed | Role of triggering receptor expressed on myeloid cells-1 in the mechanotransduction signaling pathways that link low shear stress with inflammation |
| title_short | Role of triggering receptor expressed on myeloid cells-1 in the mechanotransduction signaling pathways that link low shear stress with inflammation |
| title_sort | role of triggering receptor expressed on myeloid cells 1 in the mechanotransduction signaling pathways that link low shear stress with inflammation |
| url | https://doi.org/10.1038/s41598-023-31763-w |
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