NF-κB and its crosstalk with endoplasmic reticulum stress in atherosclerosis

Abstract

Atherosclerosis (AS) is a common cardiovascular disease with complex pathogenesis, in which multiple pathways and their interweaving regulatory mechanism remain unclear. The primary transcription factor NF-κB plays a critical role in AS via modulating the expression of a series of inflammatory mediators under various stimuli such as cytokines, microbial antigens, and intracellular stresses. Endoplasmic reticulum (ER) stress, caused by the disrupted synthesis and secretion of protein, links inflammation, metabolic signals, and other cellular processes via the unfolded protein response (UPR). Both NF-κB and ER stress share the intersection regarding their molecular regulation and function and are regarded as critical individual contributors to AS. In this review, we summarize the multiple interactions between NF-κB and ER stress activation, including the UPR, NLRP3 inflammasome, and reactive oxygen species (ROS) generation, which have been ignored in the pathogenesis of AS. Given the multiple links between NF-κB and ER stress, we speculate that the integrated network contributes to the understanding of molecular mechanisms of AS. This review aims to provide an insight into these interactions and their underlying roles in the progression of AS, highlighting potential pharmacological targets against the atherosclerotic inflammatory process.

Integration of 16S rRNA sequencing and metabolomics to investigate the modulatory effect of ginsenoside Rb1 on atherosclerosis

“…As an acute inflammatory protein, CRP can promote inflammatory reaction and atherothrombosis, and is an independent predictor of CVD [ 45 ]. NF-κB, an important nuclear transcription factor in inflammation, is activated to mediate the transcription of inflammatory cytokines thereby triggering or exacerbating AS [ 46 , 47 ]. NLRP3 inflammasome is a multi-protein complex, which is the most widely studied inflammasome.…”

Bacillus amyloliquefaciens attenuates the intestinal permeability, oxidative stress and endoplasmic reticulum stress: transcriptome and microbiome analyses in weaned piglets

“…During inflammation, ROS can mediate the activation of NF-κB, and the subsequent expression of inflammatory cytokines ( Srivastava et al, 2011 ). In recent decades, a crosstalk between NF-κB and ER stress has been found ( Li et al, 2022 ). ER stress can activate NF-κB by integrating functions of basal IKK activity, IRE1 and PERK ( Tam et al, 2012 ).…”

Anti-malarial artesunate ameliorates atherosclerosis by modulating arterial inflammatory responses via inhibiting the NF-κB–NLRP3 inflammasome pathway

“…NF-κB is considered the most critical transcription factor, and it controls the transcription of cytokines, chemokines, matrix metalloproteinases, and adhesion factors, which contribute to the pathogenesis of AS ( Evans et al, 2022 ; Li et al, 2022 ). NF-κB-targeted therapy using inhibitory NF-κB decoy oligodeoxynucleotide in a LPS/high-fat diet-induced AS mice model, which was very similar to our model, has exhibited protective activity on AS mice ( Kim et al, 2010 ).…”

“…As a well-studied transcription factor, nuclear factor κB (NF-κB) is activated by pathogen-associated molecular patterns (PAMPs) or cytokines and then primes transcription of a series of genes encoding cytokines and chemokines in macrophages ( Hu et al, 2021 ). In the past 3 decades, NF-κB has been regarded as the most critical player in AS because the genes it primed are involved in all phases of AS ( Li et al, 2022 ). In addition, NF-κB also primes mRNA expression of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) and apoptosis-associated speckle-like protein containing CARD (ASC), which form NLRP3 inflammasome to cleave pro-caspase-1 into caspase-1, by which it converts pro-interleukin 1β (pro-IL-1β) and pro-IL-18 to mature forms ( Baldrighi et al, 2017 ; Grebe et al, 2018 ).…”