TRIM47 Promotes Atherosclerosis by Activating NF-κB Signaling via IκBα Ubiquitination.

ox-LDL treatment increased TRIM47 expression in human umbilical vein endothelial cells alongside elevated inflammatory markers and reduced cell viability.

• In vitro studies used human umbilical vein endothelial cells (EC) treated with oxidized low-density lipoprotein (ox-LDL)
• TRIM47 expression was upregulated following ox-LDL treatment
• Inflammatory markers were elevated concurrent with TRIM47 upregulation
• Cell viability was reduced following ox-LDL treatment

TRIM47 overexpression exacerbated ox-LDL-induced inflammation in endothelial cells, while TRIM47 knockdown attenuated these effects.

• TRIM47 expression was modulated using siRNA knockdown and overexpression plasmids
• Overexpression of TRIM47 worsened inflammatory responses induced by ox-LDL treatment
• siRNA-mediated knockdown of TRIM47 reduced ox-LDL-induced inflammation
• Inflammation markers and NF-κB activation were assessed as outcome measures

TRIM47 mechanistically interacts directly with IκBα, promoting its ubiquitination and degradation, leading to enhanced NF-κB activation.

• TRIM47 functions as an E3 ubiquitin ligase in this pathway
• Direct interaction between TRIM47 and IκBα was demonstrated
• TRIM47-mediated ubiquitination of IκBα led to its degradation
• IκBα degradation resulted in enhanced NF-κB signaling activation
• This mechanism represents an upstream regulatory step in NF-κB-driven vascular inflammation

TRIM47 knockdown in ApoE-/- mice significantly reduced atherosclerotic plaque formation and lesion size.

• In vivo studies utilized ApoE-/- mice fed a high-fat diet
• TRIM47 knockdown was achieved using adenovirus-mediated delivery
• Atherosclerotic plaque formation was significantly reduced following TRIM47 knockdown
• Lesion size was also significantly reduced in TRIM47 knockdown animals

TRIM47 was identified as a novel regulator of atherosclerosis progression and a potential therapeutic target for atherosclerosis and related cardiovascular diseases.

• TRIM47 is described as a 'novel regulator of atherosclerosis progression'
• The regulatory mechanism operates through IκBα ubiquitination and NF-κB activation
• The findings suggested that 'TRIM47 might be a potential therapeutic target for the treatment of atherosclerosis and related cardiovascular diseases'
• The study addressed a gap in understanding upstream regulators of NF-κB signaling in atherosclerosis