Role of triggering receptor expressed on myeloid cells-1 in the mechanotransduction signaling pathways that link low shear stress with inflammation.
Role of triggering receptor expressed on myeloid cells-1 in the mechanotransduction signaling pathways that link low shear stress with inflammation.
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DOI：
10.1038/s41598-023-31763-w
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发表时间：
2023-03-21
影响因子：
4.6
通讯作者：
Chatzizisis, Yiannis S. S.
中科院分区：
文献类型：
--
作者：
Liu, Martin;Panagopoulos, Anastasios Nikolaos;Oguz, Usama M. M.;Samant, Saurabhi;Vasa, Charu Hasini;Agrawal, Devendra K. K.;Chatzizisis, Yiannis S. S.
本研究旨在探讨髓样细胞 1 (TREM-1) 上表达的触发受体在将低剪切应力与炎症联系起来的机械转导信号通路中的作用。人冠状动脉内皮细胞、人冠状动脉平滑肌细胞和THP-1单核细胞共培养并暴露于不同的内皮剪切应力（ESS）条件下：低（5±3达因/cm2）、中（10±±3达因/cm2）和高（15±±3达因/cm2）。我们发现，低 ESS 增加了培养细胞 TREM-1 的表达，导致炎症介质和基质降解酶的产生增加，而高 ESS 对 TREM-1 和炎症介质的表达没有显着影响。此外，在暴露于低ESS的内皮细胞、平滑肌细胞和单核细胞中，用siRNA抑制TREM-1转录，导致血管炎症介质和基质降解酶的产生显着减少。此外，我们还确定了响应低 ESS 而上调 TREM-1 基因表达的转录因子。据我们所知，这是第一项使用复杂的动脉粥样硬化体外模型来研究低 ESS、TREM-1 和炎症之间的病理生理学关联和分子途径的研究。未来对动物和人类的研究有必要探讨 TREM-1 抑制剂作为辅助抗动脉粥样硬化疗法的潜力。
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.
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影响因子：
37.8
作者：
Chatzizisis, Yiannis S.;Jonas, Michael;Stone, Peter H.
通讯作者：
Stone, Peter H.
影响因子：
15.1
作者：
Weigelt, Karin;Carvalho, Livia A.;Drexhage, Hemmo A.
通讯作者：
Drexhage, Hemmo A.
影响因子：
37.8
作者：
Chatzizisis YS;Baker AB;Sukhova GK;Koskinas KC;Papafaklis MI;Beigel R;Jonas M;Coskun AU;Stone BV;Maynard C;Shi GP;Libby P;Feldman CL;Edelman ER;Stone PH
通讯作者：
Stone PH
影响因子：
5.4
作者：
Zeng, Heng;Ornatowska, Magdalena;Sadikot, Ruxana T.
通讯作者：
Sadikot, Ruxana T.
沉默髓样细胞-1 上表达的触发受体会损害巨噬细胞中氧化低密度脂蛋白的炎症反应。
影响因子：
5.1
作者：
Li, Houxuan;Hong, Feifei;Yan, Fuhua
通讯作者：
Yan, Fuhua