Neutrophil Extracellular Traps in Atherosclerosis and Atherothrombosis

Döring, Yvonne; Soehnlein, Oliver; Weber, Christian

doi:10.1161/circresaha.116.309692

Cited by 359 publications

(270 citation statements)

References 102 publications

(132 reference statements)

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“…This point, discussed by Döring et al, raises questions on the precise mechanisms implicated in the detrimental role of neutrophils on plaque progression, either via NETosis, or/and specific neutrophil proteases that affect inflammatory cytokines production and maturation. 34 Previous reports implied a direct role for neutrophils in superficial erosion and in endothelial desquamation. Ferrante et al showed that systemic myeloperoxidase (MPO) levels―a heme protein most abundantly expressed in azurophilic granules in neutrophils―rose significantly in patients with eroded plaques compared with patients presenting with ruptured plaque, as determined by OCT. 35 In vitro , ROS derived from MPO release can promote EC apoptosis 36 and MPO-containing neutrophil microparticles cause damage of vascular ECs and disruption of the endothelial barrier.…”

Section: A Special Role For Granulocytes and Neutrophil Extracellularmentioning

confidence: 99%

Mechanisms of erosion of atherosclerotic plaques

Quillard

Franck²,

Mawson³

et al. 2017

Current Opinion in Lipidology

134

118

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Purpose of review This review explores the mechanisms of superficial intimal erosion, a common cause of thrombotic complications of atherosclerosis. Recent findings Human coronary artery atheroma that give rise to thrombosis due to erosion differ diametrically from those associated with fibrous cap rupture. Eroded lesions characteristically contain few inflammatory cells, abundant extracellular matrix, and neutrophil extracellular traps (NETs). Innate immune mechanisms such as engagement of Toll-like receptor 2 (TLR2) on cultured endothelial cells (EC) can impair their viability, attachment, and ability to recover a wound. Hyaluronan fragments may serve as endogenous TLR2 ligands. Mouse experiments demonstrate that flow disturbance in arteries with neointimas tailored to resemble features of human eroded plaques disturbs EC barrier function, impairs EC viability, recruits neutrophils, and provokes EC desquamation, NET formation, and thrombosis in a TLR2-dependent manner. Summary Mechanisms of erosion have received much less attention than those that provoke plaque rupture. Intensive statin treatment changes the characteristic of plaques that render them less susceptible to rupture. Thus, erosion may contribute importantly to the current residual burden of risk. Understanding the mechanisms of erosion may inform the development and deployment of novel therapies to combat the remaining atherothrombotic risk in the statin era.

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Section: A Special Role For Granulocytes and Neutrophil Extracellularmentioning

confidence: 99%

Mechanisms of erosion of atherosclerotic plaques

Quillard

Franck²,

Mawson³

et al. 2017

Current Opinion in Lipidology

134

118

View full text Add to dashboard Cite

show abstract

“…In turn, the activation of PMN could generate structures known as neutrophil extracellular traps (NETs), comprised of strands of unwound DNA released by the dying granulocytes. 69 This uncoiled DNA becomes decorated with proteases, tissue factor, and pro-oxidant enzymes that could propagate local amplification of an innate immune response, thrombin activation, fibrin generation, and entrap further platelets and fibrin strands in an evolving thrombus 49 .…”

Section: Plaque Erosionmentioning

confidence: 99%

Acute Coronary Syndromes

2017

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Well into the 21st century, we still triage acute myocardial infarction based on the presence or absence of ST segment elevation, a century-old technology. Meanwhile, we have learned a great deal regarding the pathophysiology and mechanisms of acute coronary syndromes (ACS) at clinical, pathological, cellular, and molecular levels. Contemporary imaging studies have shed new light into the mechanisms of ACS. This review discusses these advances and their implications for clinical management of the ACS for the future. Plaque rupture has dominated our thinking about ACS pathophysiology for decades. Yet, current evidence suggests that a sole focus on plaque rupture vastly oversimplifies this complex collection of diseases, and obscures other mechanisms that may mandate different management strategies. We propose to segment coronary artery thrombosis due to plaque rupture into cases with or without signs of concomitant inflammation. This distinction may have substantial therapeutic implications as direct anti-inflammatory interventions for atherosclerosis emerge. Coronary artery thrombosis due to plaque erosion may be on the rise in an era of intense lipid lowering. Identification of patients with of ACS due to erosion may permit a less invasive approach to management than the current standard of care. We also now recognize ACS that occur without apparent epicardial coronary artery thrombus or stenosis. Such events may arise from spasm, microvascular disease, or other pathways. Emerging management strategies may likewise apply selectively to this category of ACS. We advocate this more mechanistic approach to the categorization of ACS to provide a framework for future tailoring, triage, and therapy for patients in a more personalized and precise manner.

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“…Recent studies, however, have provided substantial evidence of their participation in the pathogenesis of atherosclerosis and atherosclerosis-related CV events. 41,42 Additionally, the presence of NETs in human atherosclerotic vessel biopsies was observed in proximity and correlated with apoptotic endothelial cells 43 While the role of neutrophils in thrombosis was known, more recently become evident that TF is also present on NETs released by neutrophils isolated from blood drawn near occluded arteries in the cases of acute coronary syndromes, indicating their procoagulant properties. The invading bacteria get trapped in NETs and as a result, are killed or their virulence factors get degraded.…”

Section: Role Of Neutrophilsmentioning

confidence: 99%

Atherosclerosis: Beyond the lipid storage hypothesis. The role of autoimmunity

Cinoku

Mavragani

Moutsopoulos

2020

Eur J Clin Investigation

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Atherosclerosis has long been considered as a lipid storage disease. Recent data suggest that autoimmune mechanisms seem to be involved in the pathophysiology of atherosclerosis. The presence of activated endothelial vascular cells, neutrophils, macrophages, T and to a lesser extent B cells in atherosclerotic plaques, together with the proinflammatory cytokine burden suggest mobilization of both innate and adaptive immune pathways in atherosclerosis pathobiology. The development of antibodies to oxidized low-density lipoprotein (ox-LDL), the experimental induction of atherosclerosis either via the transfer of T cells or immunization with autoantigens such as β2 glycoprotein Ι (β2-GPI) and heat shock proteins (HSP) further support the autoimmune nature of atherosclerosis. However, classical immunosuppressive and immune-modulatory drugs, successfully used in the therapy of autoimmune rheumatic diseases have shown limited benefits so far in the treatment of atherosclerosis. K E Y W O R D Satherosclerosis, autoimmune disease, autoimmune response, oxidized form of low-density lipoprotein

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Neutrophil Extracellular Traps in Atherosclerosis and Atherothrombosis

Cited by 359 publications

References 102 publications

Mechanisms of erosion of atherosclerotic plaques

Mechanisms of erosion of atherosclerotic plaques

Acute Coronary Syndromes

Atherosclerosis: Beyond the lipid storage hypothesis. The role of autoimmunity

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