Recent advances of mechanosensitive genes in vascular endothelial cells for the formation and treatment of atherosclerosis

Li, Shuyu; Xu, Zichen; Wang, Yi; Chen, Lizhao; Wang, Xiangxiu; Zhou, Yanghao; Lei, Daoxi; Zang, Guangchao; Wang, Guixue

doi:10.1016/j.gendis.2023.06.016

Cited by 2 publications

(1 citation statement)

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“…Oxidative stress, caused by the accumulation of intracellular ROS, can lead to various diseases such as atherosclerosis, diabetes mellitus, Alzheimer's disease, and Parkinson's disease due to VEC proinflammation and dysfunction. (Li et al 2023 ; Ravi et al 2024 ; Wang et al 2023 ). Intracellular ROS production contributes to the pro-inflammatory and dysfunctional state of VECs through the activation of NF-κB (Zhenyukh et al 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Vascular endothelial dysfunction induced by 3-bromofluoranthene via MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation

Lee,

Wu,

Yang

et al. 2024

Arch Toxicol

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Abstract3-Bromofluoranthene (3-BrFlu) is the secondary metabolite of fluoranthene, which is classified as a polycyclic aromatic hydrocarbon, through bromination and exists in the fine particulate matter of air pollutants. Endothelial dysfunction plays a critical role in the pathogenesis of cardiovascular and vascular diseases. Little is known about the molecular mechanism of 3-BrFlu on endothelial dysfunction in vivo and in vitro assay. In the present study, 3-BrFlu included concentration-dependent changes in ectopic angiogenesis of the sub-intestinal vein and dilation of the dorsal aorta in zebrafish. Disruption of vascular endothelial integrity and up-regulation of vascular endothelial permeability were also induced by 3-BrFlu in a concentration-dependent manner through pro-inflammatory responses in vascular endothelial cells, namely, SVEC4-10 cells. Generation of pro-inflammatory mediator PGE2 was induced by 3-BrFlu through COX2 expression. Expression of COX2 and generation of pro-inflammatory cytokines, including TNFα and IL-6, were induced by 3-BrFlu through phosphorylation of NF-κB p65, which was mediated by phosphorylation of MAPK, including p38 MAPK, ERK and JNK. Furthermore, generation of intracellular ROS was induced by 3-BrFlu, which is associated with the down-regulated activities of the antioxidant enzyme (AOE), including SOD and catalase. We also found that 3-BrFlu up-regulated expression of the AOE and HO-1 induced by 3-BrFlu through Nrf-2 expression. However, the 3-BrFlu-induced upregulation of AOE and HO-1 expression could not be revised the responses of vascular endothelial dysfunction. In conclusion, 3-BrFlu is a hazardous substance that results in vascular endothelial dysfunction through the MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation.

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