Interleukin-1 in Coronary Artery Disease

Abstract

Cardiovascular disease is the leading cause of mortality worldwide. Inflammation has long been established as a key component in the pathophysiology of coronary artery disease. The interleukin-1 family consists of 11 members that regulate the inflammatory response through both pro- and anti-inflammatory properties with the Nod-like receptor (NLR) family pyrin domain containing 3 inflammasome having a pivotal role in the process of converting interleukin-1 beta and interleukin-18, two key inflammatory mediators, into their mature forms. Interleukin-1 affects various cell types that participate in the pathogenesis of atherosclerosis as it enhances the expression of leukocyte adhesion molecules on the surface of endothelial cells augment the permeability of the endothelial cell barrier, attracting monocytes and macrophages into the vessel wall and aids the migration of smooth muscle cells toward atheroma. It also enhances the aggregation of low-density lipoprotein particles in endothelium and smooth muscle cells and exhibits procoagulant activity by inducing synthesis, cell-surface expression and release of tissue factor in endothelial cells, promoting platelet adhesion. The value of interleukin-1 as a diagnostic biomarker is currently limited but interleukin-1 beta, interleukin-18 and interleukin-37 have shown promising data regarding their prognostic value in coronary artery disease. Importantly, target anti-inflammatory treatments have shown promising results regarding atherosclerosis progression and cardiovascular events. In this review article we focus on the immense role of interleukin-1 in atherosclerosis progression, inflammation cascade and in the clinical application of target anti-inflammatory treatments.

Prognostic significance of IL‐18 in acute coronary syndrome patients

“…Our findings align with the prevailing understanding that the outcome of ACS is intricately linked to inflammatory processes 3,37 . Indeed, IL‐18 has shown promising potential as a prognostic biomarker in the context of ACS 12,38 . Multiple studies have emphasized circulating IL‐18 as a robust predictor of cardiovascular outcomes in ACS, consistent with our findings 14,15,39 .…”

“…IL‐18, a proinflammatory cytokine implicated in the process of pyroptosis, is synthesized by various immune cells, such as macrophages, dendritic cells, and epithelial cells. Its biological effects extend to T cells, natural killer cells, and neutrophils, inciting the generation of interferon‐gamma and tumor necrosis factor‐alpha 12,30 . IL‐18 plays an intricate role in inflammatory conditions, encompassing autoimmune disorders, infectious diseases, and atherosclerosis 31 .…”

“…IL‐1β contributes locally to vascular inflammation and destabilization of atherosclerotic plaques, targeted by drugs like canakinumab in ACS 9,10 . IL‐18, akin to IL‐1β, sparks inflammation in atherosclerosis and plaque instability 11,12 . While IL‐1β is a target for anti‐inflammatory therapies, IL‐18's role is intricate.…”

Lipoprotein(a) in Atherosclerotic Diseases: From Pathophysiology to Diagnosis and Treatment

“…More precisely, this effect is mediated by oxidized phospholipids (OxPLs) bound to apo(a), and their interaction with apo(a) requires the lysine-binding site in KIV10 [ 18 , 91 ]. Except for IL-8, Lp(a) also increases expression of interleukin-1β (IL-1β) [ 92 ] and tumor necrosis factor-α (TNF-α) by macrophages, multiplying inflammation of the arterial wall [ 42 , 87 , 88 ].…”

Integrating Network Pharmacology And Experimental Verification To Explore The Mechanism Of Qionggui Power Against Atherosclerosis

“…Macrophage is one of the key cell types that contributes to arterial inflammation. As the most abundant leukocyte in atherosclerotic lesions, macrophage decisively determines the inflammatory environment in the plague particularly by secreting inflammation-related cytokines, such as IL1, IL6, and TNFα [26, 27] . Clinical agents that antagonize these cytokines have proven considerable effectiveness in reducing cardiovascular events [28, 29] .…”