Role of triggering receptor expressed on myeloid cells-1 in the mechanotransduction signaling pathways that link low shear stress with inflammation.

Martin Liu, Anastasios Nikolaos Panagopoulos, Usama M Oguz, Saurabhi Samant, Charu Hasini Vasa, Devendra K Agrawal, Yiannis S Chatzizisis

Scientific reports 2023 Mar 21

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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. © 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Citation

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. 2023 Mar 21;13(1):4656