Triggering receptor expressed on myeloid cells-1 (TREM-1) inhibition in atherosclerosis

Panagopoulos, Anastasios; Samant, Saurabhi; Bakhos, Jules Joel; Liu, Martin; Khan, Behram; Makadia, Janaki; Fayaz, Muhammad; Kievit, Forrest M.; Agrawal, Devendra K.; Chatzizisis, Yiannis S.

doi:10.1016/j.pharmthera.2022.108182

Cited by 12 publications

(17 citation statements)

References 81 publications

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“…In the present study, we used a co-culture model consisting of endothelial cells, monocytes and smooth muscle cells, to investigate the intermediate role of TREM-1 in the molecular pathways that link low shear stress with inflammation. To delineate the role of TREM-1 between low ESS and inflammation, we eliminated the confounding role of LDL, since LDL has been found to promote inflammation through the TREM-1 pathways independently of shear stress 2 . 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 markers.…”

Section: Discussionmentioning

confidence: 99%

“…TREM-1 is an activating receptor expressed on the surface of endothelial cells, immune cells (neutrophils, monocytes macrophages) and vascular smooth muscle cells 2 . TREM-1 activation amplifies the vascular inflammatory response through increased production of pro-inflammatory molecules, production of matrix-degrading enzymes and recruitment of inflammatory cells.…”

Section: Discussionmentioning

confidence: 99%

“…TREM-1 activation amplifies the vascular inflammatory response through increased production of pro-inflammatory molecules, production of matrix-degrading enzymes and recruitment of inflammatory cells. Several studies have highlighted the implication of TREM-1 activation in various pathophysiologic processes that contribute to atherosclerosis and its complications such as endothelial dysfunction, inflammatory lipid accumulation, plaque destabilization and increased thrombogenicity 2 . However, to date, no study has focused on the association of low ESS with TREM-1 activation.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Triggering receptor expressed on myeloid cells-1 (TREM-1) is an inflammatory mediator belonging to the immunoglobulin family and has been found to be expressed on the surface of all the cell types involved in atherosclerosis (endothelial cells, white blood cells, vascular smooth muscle cells and platelets) 2 . Studies have shown that TREM-1 plays pivotal role in the sterile inflammation of atherosclerosis 2 . One could hypothesize that TREM-1 plays an intermediate role in the association between low ESS with inflammation, however the detailed mechanotransduction signaling mechanisms that link low ESS with TREM-1 remain unknown.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

Panagopoulos

Oguz

et al. 2023

Sci Rep

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Liu

Panagopoulos

Oguz

et al. 2023

Sci Rep

Self Cite

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Role of oncostatin-M in ECM remodeling and plaque vulnerability

2023

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Atherosclerosis is a multifactorial inflammatory disease characterized by the development of plaque formation leading to occlusion of the vessel and hypoxia of the tissue supplied by the vessel. Chronic inflammation and altered collagen expression render stable plaque to unstable and increase plaque vulnerability. Thinned and weakened fibrous cap results in plaque rupture and formation of thrombosis and emboli formation leading to acute ischemic events such as stroke and myocardial infarction. Inflammatory mediators including TREM-1, TLRs, MMPs, and immune cells play a critical role in plaque vulnerability. Among the other inflammatory mediators, oncostatin-M (OSM), a pro-inflammatory cytokine, play an important role in the development and progression of atherosclerosis, however, the role of OSM in plaque vulnerability and extracellular matrix remodeling (ECM) is not well understood and studied. Since ECM remodeling plays an important role in atherosclerosis and plaque vulnerability, a detailed investigation on the role of OSM in ECM remodeling and plaque vulnerability is critical. This is important because the role of OSM has been discussed in the context of proliferation of vascular smooth muscle cells and regulation of cytokine expression but the role of OSM is scarcely discussed in relation to ECM remodeling and plaque vulnerability. This review focuses on critically discussing the role of OSM in ECM remodeling and plaque vulnerability.

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TREM1: Activation, signaling, cancer and therapy

Li,

Cai,

et al. 2024

Pharmacological Research

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Triggering receptor expressed on myeloid cells-1 (TREM-1) inhibition in atherosclerosis

Cited by 12 publications

References 81 publications

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

Role of oncostatin-M in ECM remodeling and plaque vulnerability

TREM1: Activation, signaling, cancer and therapy

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