Inflammation and atherosclerosis: signaling pathways and therapeutic intervention

Abstract

Atherosclerosis is a chronic inflammatory vascular disease driven by traditional and nontraditional risk factors. Genome-wide association combined with clonal lineage tracing and clinical trials have demonstrated that innate and adaptive immune responses can promote or quell atherosclerosis. Several signaling pathways, that are associated with the inflammatory response, have been implicated within atherosclerosis such as NLRP3 inflammasome, toll-like receptors, proprotein convertase subtilisin/kexin type 9, Notch and Wnt signaling pathways, which are of importance for atherosclerosis development and regression. Targeting inflammatory pathways, especially the NLRP3 inflammasome pathway and its regulated inflammatory cytokine interleukin-1β, could represent an attractive new route for the treatment of atherosclerotic diseases. Herein, we summarize the knowledge on cellular participants and key inflammatory signaling pathways in atherosclerosis, and discuss the preclinical studies targeting these key pathways for atherosclerosis, the clinical trials that are going to target some of these processes, and the effects of quelling inflammation and atherosclerosis in the clinic.

Low-density lipoprotein particles in atherosclerosis

“…Of note, statins upregulate LDLR through sterol regulatory binding protein-2, which also enhance the expression of PCSK9. Accumulating evidence have demonstrated that PCSK9 induces the formation of LDLR-PCSK9 complex, leading to the degradation of LDLR in lysosomes, thereby reducing LDLR recycling and LDL-P clearance ( Guo et al, 2020 ; Kong et al, 2022 ).…”

“…The pathological basis of CVD is atherosclerosis, a disease of arteries causing myocardial infarction, stroke, and other complications ( Libby et al, 2019 ). Atherosclerosis occurs primarily in the subendothelial space of the middle and large arteries, where blood flow is disturbed and/or bifurcated ( Siasos et al, 2018 ; Kong et al, 2022 ). Accumulating evidence have demonstrated that many risk factors including hyperlipidemia, hypertension, oxidative stress, inflammation, endothelium dysfunction as well as high-calorie diet and unhealthy habits, such as smoking, contribute to the initiation and progression of atherosclerotic CVD (ASCVD) ( Lee and Cooke, 2011 ).…”

The Protective Effects of Neoastilbin on Monosodium Urate Stimulated THP-1-Derived Macrophages and Gouty Arthritis in Mice through NF-κB and NLRP3 Inflammasome Pathways

“…In the present study, neoastilbin inhibited GA, including inflammatory cytokine release and inflammatory cell infiltration into the lesion site, mediated by the suppression of NF-κB and NLRP3 inflammasome pathways in THP-1-derived macrophages and GA mice. Considering that the NF-κB and NLRP3 inflammasome pathways are related to the development of many inflammatory diseases, neoastilbin may have potential clinical application value in gout, autoinflammatory syndrome or other NLRP3-driven diseases [ 41 , 42 , 43 , 44 ].…”

High-Risk Coronary Plaque Features: A Narrative Review

“…Locally, lipid accumulation leads to free radical formation, endothelial activation and inflammation, all resulting in an imbalance in reactive oxygen species, which transform monocytes into foam cells [ 75 ]. This process involves multiple cell types, both intracellular and extracellular reactive oxygen and nitrogen species and complex signalling pathways, including the NLRP3 inflammasome pathway, the Wnt and Notch pathways, Toll-like receptors and proprotein convertase subtilisin/kexin type 9 [ 75 , 76 ]. Systemic biomarkers of inflammation, such as high-sensitivity C-reactive protein and interleukin-6, are both associated with risk of ACS [ 77 ].…”