Abstract
Systemic lupus erythematosus (SLE) is an autoimmune syndrome of unknown etiology, characterized by multi-organ inflammation and clinical heterogeneity. SLE affects mostly women and is associated with a high risk of cardiovascular disease. As the therapeutic management of SLE improved, a pattern of early atherosclerotic disease became one of the hallmarks of late disease morbidity and mortality. Neutrophils emerged as important players in SLE pathogenesis and they are associated with increased risk of developing atherosclerotic disease and vascular damage. Enhanced neutrophil extracellular trap (NET) formation was linked to vasculopathy in both SLE and non-SLE subjects and may promote enhanced coronary plaque formation and lipoprotein dysregulation. Foundational work provided insight into the complex relationship between NETs and immune and tissue resident cells within the diseased artery. In this review, we highlight the mechanistic link between neutrophils, NETs, and atherosclerosis within the context of both SLE and non-SLE subjects. We aim to identify actionable pathways that will drive future research toward translational therapeutics, with the ultimate goal of preventing early morbidity and mortality in SLE.
Highlights
Atherosclerosis, a common cause of morbidity and mortality in the general population [1], continues to be a hotbed of translational and clinical research
This association is striking in systemic lupus erythematosus (SLE), where observational and epidemiologic studies described up to 50-fold increased risk of developing cardiovascular disease compared with non-SLE patients [4,5]
We provide an overview of SLE and atherosclerosis, discuss the role of neutrophils and neutrophil extracellular traps (NETs) in atherosclerosis, and provide SLE-specific evidence of NETs mediating atherosclerotic disease
Summary
Atherosclerosis, a common cause of morbidity and mortality in the general population [1], continues to be a hotbed of translational and clinical research. Consistent with this, patients with various autoimmune diseases have a clear predisposition toward the development of atherosclerosis [3]. This association is striking in systemic lupus erythematosus (SLE), where observational and epidemiologic studies described up to 50-fold increased risk of developing cardiovascular disease compared with non-SLE patients [4,5]. Neutrophils were implicated in the inflammation observed in the pathogenesis of both athero-embolic disease and SLE pathophysiology [6]. Understanding how neutrophils mediate atherosclerosis may provide an understanding of actionable pathways in both SLE and non-SLE subjects and, could contribute to improving patient management and clinical outcomes. We provide an overview of SLE and atherosclerosis, discuss the role of neutrophils and neutrophil extracellular traps (NETs) in atherosclerosis, and provide SLE-specific evidence of NETs mediating atherosclerotic disease
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