Silencing triggering receptor expressed on myeloid cells-1 inhibits vascular smooth muscle cell inflammation mediated by trimethylamine N-oxide by regulating the nuclear factor-kappa B signaling pathway

Tan Wenyun, Jing Shuyan, Wang Ruirui, Wang Gang

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Journal of Chongqing Medical University ›› 2025, Vol. 50 ›› Issue (03) : 337-343. DOI: 10.13406/j.cnki.cyxb.003648
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Silencing triggering receptor expressed on myeloid cells-1 inhibits vascular smooth muscle cell inflammation mediated by trimethylamine N-oxide by regulating the nuclear factor-kappa B signaling pathway

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Abstract

Objective To investigate the role and possible mechanism of triggering receptor expressed on myeloid cells-1（TREM-1） in the inflammatory response of rat vascular smooth muscle cells（VSMCs） mediated by trimethylamine N-oxide（TMAO）. Methods VSMCs were treated with TMAO at different concentrations（0，100，300，600，900，1 200，1 500 μmol/L） for 24 hours. VSMCs were transfected with the siRNA interference plasmid targeting the TREM-1 gene（si-TREM-1） and its negative control interference plasmid（si-NC），and 600 μmol/L TMAO was used to induce inflammatory response in VSMCs，combined with the intervention with the nuclear factor-kappa B（NF-κB） activator phorbol myristate acetate（PMA） for 24 hours. CCK-8 assay was used to measure cell proliferative activity；ELISA was used to measure the levels of interleukin-1β（IL-1β），interleukin-6（IL-6），and tumor necrosis factor-α（TNF-α） in cell supernatant；qRT-PCR was used to measure the mRNA expression levels of TREM-1，cyclooxygenase-2（COX-2），intercellular adhesion molecule-1（ICAM-1），IL-1β，IL-6，and TNF-α in cells，and Western blot was used to measure the protein expression levels of TREM-1，COX-2，ICAM-1，NF-κB p65，and p-NF-κB p65（Ser536） in cells. Results Treatment with TMAO at different concentrations had no significant impact on the proliferative activity of VSMCs（P=0.375），but it significantly upregulated the levels of IL-1β，IL-6，and TNF-α in supernatant and the mRNA and protein expression levels of TREM-1，COX-2，and ICAM-1 in cells（all P<0.01） in a concentration-dependent manner. Silencing of the TREM-1 gene significantly inhibited the increases in the levels of IL-1β，IL-6，and TNF-α in the supernatant of VSMCs induced by TMAO，and it also suppressed the upregulation of the mRNA expression levels of COX-2，ICAM-1，IL-1β，IL-6，and TNF-α and the ratio of p-NF-kB p65/NF-kB p65 in VSMCs（all P<0.01）. However，PMA intervention significantly reversed the role of silencing the TREM-1 gene on TMAO-induced inflammatory response in VSMCs. Conclusion Silencing of the TREM-1 gene can inhibit TMAO-induced inflammatory response in VSMCs，possibly by inhibiting the activation of the NF-κB pathway.

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trimethylamine N-oxide / vascular smooth muscle cells / inflammatory response / triggering receptor expressed on myeloid cells-1 / nuclear factor-kappa B pathway

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Tan Wenyun , Jing Shuyan , Wang Ruirui , et al. Silencing triggering receptor expressed on myeloid cells-1 inhibits vascular smooth muscle cell inflammation mediated by trimethylamine N-oxide by regulating the nuclear factor-kappa B signaling pathway. Journal of Chongqing Medical University. 2025, 50(03): 337-343 https://doi.org/10.13406/j.cnki.cyxb.003648

References

List( Publishing order | Descend order by publishing year | Descend order by cited within ) Chart analysis
1
习婧媛，韩　颖，陈湘. 2010—2019年中国居民四类慢性非传染病的死亡趋势及差别分解分析[J]. 现代预防医学，2022，49（12）：2119-2125.
Xi JY， Han Y， Chen X. Trend and differential decomposition analysis of four types of chronic noncommunicable diseases mortality among Chinese residents，2010-2019[J]. Mod Prev Med，2022，49（12）：2119-2125.
本文引用 [1]
2
马伟利，蔡　颖，宝凤梅，等. 芪苈强心胶囊联合西药治疗高龄慢性心力衰竭的疗效及对NT-proBNP、TNF-α、IL-6水平的影响[J]. 中药材，2020，6（11）：2818-2821.
Ma WL， Cai Y， Bao FM，et al. The efficacy of Qi Li Qiang Xin Capsules combined with Western medicine in the treatment of elderly patients with chronic heart failure and its impact on NT-proBNP，TNF-α，IL-6 levels of influence [J]. Chin Med Mater，2020，6（11）：2818-2821.
本文引用 [1]
3
Shi J， Yang Y， Cheng AY，et al. Metabolism of vascular smooth muscle cells in vascular diseases[J]. Am J Physiol Heart Circ Physiol，2020，319（3）：H613-H631.
本文引用 [1]
4
Zhang W， Zhao JJ， Deng L，et al. INKILN is a novel long noncoding RNA promoting vascular smooth muscle inflammation via scaffolding MKL1 and USP10[J]. Circulation，2023，148（1）：47-67.
本文引用 [1]
5
Canyelles M， Borràs C， Rotllan N，et al. Gut microbiota-derived TMAO：a causal factor promoting atherosclerotic cardiovascular disease?[J]. Int J Mol Sci，2023，24（3）：1940.
本文引用 [1]
6
李亚梦，崔美泽，孙　婧，等. 肠道菌群及其代谢产物氧化三甲胺：冠心病治疗的新靶点[J]. 生物工程学报，2021，37（11）：3745-3756.
Li YM， Cui MZ， Sun J，et al. Gut microbiota and its metabolite trimethylamine-N-oxide（TMAO）：a novel regulator in coronary artery disease[J]. Chin J Biotechnol，2021，37（11）：3745-3756.
7
Zhang YX， Wang Y， Ke BB，et al. TMAO：how gut microbiota contributes to heart failure[J]. Transl Res，2021，228：109-125.
本文引用 [1]
8
Zhang XH， Zheng B， Zhao LD，et al. KLF4-PFKFB3-driven glycolysis is essential for phenotypic switching of vascular smooth muscle cells[J]. Commun Biol，2022，5（1）：1332.
本文引用 [1]
9
Santiago-Hernandez A， Martinez PJ， Agudiez M，et al. Metabolic alterations identified in urine，plasma and aortic smooth muscle cells reflect cardiovascular risk in patients with programmed coronary artery bypass grafting[J]. Antioxidants，2021，10（9）：1369.
本文引用 [1]
10
Panagopoulos A， Samant S， Bakhos JJ，et al. Triggering receptor expressed on myeloid cells-1（TREM-1） inhibition in atherosclerosis[J]. Pharmacol Ther，2022，238：108182.
本文引用 [1]
11
Zhou HX， Wang Y， Zhou QH，et al. Down-regulation of protein kinase C-ε by prolonged incubation with PMA inhibits the proliferation of vascular smooth muscle cells[J]. Cell Physiol Biochem，2016，40（1/2）：379-390.
本文引用 [1]
12
Henein MY， Vancheri S， Longo G，et al. The role of inflammation in cardiovascular disease[J]. Int J Mol Sci，2022，23（21）：12906.
本文引用 [1]
13
Ma SR， Tong Q， Lin Y，et al. Berberine treats atherosclerosis via a vitamine-like effect down-regulating Choline-TMA-TMAO production pathway in gut microbiota[J]. Signal Transduct Target Ther，2022，7（1）：207.
本文引用 [1]
14
Chen ML， Zhu XH， Ran L，et al. Trimethylamine-N-oxide induces vascular inflammation by activating the NLRP3 inflammasome through the SIRT3-SOD2-mtROS signaling pathway[J]. J Am Heart Assoc，2017，6（9）：e006347.
本文引用 [1]
15
Shi GX， Zeng LX， Shi JL，et al. Trimethylamine N-oxide promotes atherosclerosis by regulating low-density lipoprotein-induced autophagy in vascular smooth muscle cells through PI3K/AKT/mTOR pathway[J]. Int Heart J，2023，64（3）：462-469.
本文引用 [1]
16
Vandestienne M， Zhang YJ， Santos-Zas I，et al. TREM-1 orchestrates angiotensin II-induced monocyte trafficking and promotes experimental abdominal aortic aneurysm[J]. J Clin Invest，2021，131（2）：e142468.
本文引用 [1]
17
Wang F， Li C， Ding FH，et al. Increased serum TREM-1 level is associated with in-stent restenosis，and activation of TREM-1 promotes inflammation，proliferation and migration in vascular smooth muscle cells[J]. Atherosclerosis，2017，267：10-18.
本文引用 [1]
18
Li C， Zhang YJ， Sun Y， Wang HX，et al The effect of retinoic acid on lipopolysaccharide induced vascular inflammation and oxidative stress through the TLR 4 /NF-κB pathway Chinese[J]. Journal of Clinical Anatomy，2022，40（3）：303-308.
本文引用 [1]
19
Rao S， Huang J， Shen Z，et al Inhibition of TREM-1 attenuates inflammation and lipid accumulation in diet-induced nonalcoholic fatty liver disease[J]. Cell Biochem，2019，120（7）：11867-11877.
本文引用 [1]
20
El Habhab A， Altamimy R， Abbas M，et al. Significance of neutrophil microparticles in ischaemia-reperfusion: pro-inflammatory effectors of endothelial senescence and vascular dysfunction[J]. Cell Mol Med，2020，24（13）：7266-7281.
本文引用 [1]

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