Neutrophil extracellular traps(NETs)have emerged as key mediators of cardiovascular diseases(CVDs),linking innate immune activation to vascular injury,thrombosis,and maladaptive remodeling.This review synthesizes rece...Neutrophil extracellular traps(NETs)have emerged as key mediators of cardiovascular diseases(CVDs),linking innate immune activation to vascular injury,thrombosis,and maladaptive remodeling.This review synthesizes recent insights into the molecular and cellular pathways driving NET formation,including post-translational modifications,metabolic reprogramming,inflammasome signaling,and autophagy.It highlights the role of NETs in atherosclerosis,thrombosis,myocardial ischemia-reperfusion injury,and hypertension,emphasizing common control points such as peptidylarginine deiminase 4(PAD4)-dependent histone citrullination and nicotinamide adenine dinucleotide phosphate oxidases 2(NOX2)-mediated oxidative stress.Mechanistic interpretation of circulating biomarkers,includingmyeloperoxidase(MPO)-DNA complexes,citrullinated histoneH3,and cell-free DNA,provides a translational bridge between NET biology and patient stratification.Therapeutic strategies targeting NETs are examined through three main approaches:inhibition of NET initiation,enhancement of chromatin clearance,and neutralization of toxic extracellular components,with attention to both established and emerging interventions.In contrast to previous reviews,this study highlights the novelty of a mechano-therapeutic framework by providing a mechanistic roadmap linking NET formation pathways to therapeutic targeting in cardiovascular disease.Moving forward,integrating mechanistic information with biomarker discovery,precision profiling,and targeted therapies offers innovative strategies to reduce vascular inflammation and improve outcomes in cardiovascular disease.展开更多
Sepsis is a life-threatening condition caused by a dysregulated host response to infection,with its high mortality closely linked to excessive neutrophil activation and the release of neutrophil extracellular traps(NE...Sepsis is a life-threatening condition caused by a dysregulated host response to infection,with its high mortality closely linked to excessive neutrophil activation and the release of neutrophil extracellular traps(NETs).While NETs play a critical role in antimicrobial immunity,their overproduction can lead to tissue damage and multiple organ dysfunction,exacerbating the pathological progression of sepsis.This study focuses on the role of palmitoyltransferase ZDHHC18 in sepsis,proposing that it may regulate the formation of neutrophil NETs through palmitoylation,thereby promoting the onset of sepsis.Currently,there is no research,domestically or internationally,on the role of ZDHHC18 in NETs during sepsis.Therefore,exploring potential therapeutic strategies—such as inhibiting ZDHHC18 to mitigate the pathological effects of sepsis—could provide new insights for treating sepsis-related inflammatory diseases.展开更多
文摘Neutrophil extracellular traps(NETs)have emerged as key mediators of cardiovascular diseases(CVDs),linking innate immune activation to vascular injury,thrombosis,and maladaptive remodeling.This review synthesizes recent insights into the molecular and cellular pathways driving NET formation,including post-translational modifications,metabolic reprogramming,inflammasome signaling,and autophagy.It highlights the role of NETs in atherosclerosis,thrombosis,myocardial ischemia-reperfusion injury,and hypertension,emphasizing common control points such as peptidylarginine deiminase 4(PAD4)-dependent histone citrullination and nicotinamide adenine dinucleotide phosphate oxidases 2(NOX2)-mediated oxidative stress.Mechanistic interpretation of circulating biomarkers,includingmyeloperoxidase(MPO)-DNA complexes,citrullinated histoneH3,and cell-free DNA,provides a translational bridge between NET biology and patient stratification.Therapeutic strategies targeting NETs are examined through three main approaches:inhibition of NET initiation,enhancement of chromatin clearance,and neutralization of toxic extracellular components,with attention to both established and emerging interventions.In contrast to previous reviews,this study highlights the novelty of a mechano-therapeutic framework by providing a mechanistic roadmap linking NET formation pathways to therapeutic targeting in cardiovascular disease.Moving forward,integrating mechanistic information with biomarker discovery,precision profiling,and targeted therapies offers innovative strategies to reduce vascular inflammation and improve outcomes in cardiovascular disease.
文摘Sepsis is a life-threatening condition caused by a dysregulated host response to infection,with its high mortality closely linked to excessive neutrophil activation and the release of neutrophil extracellular traps(NETs).While NETs play a critical role in antimicrobial immunity,their overproduction can lead to tissue damage and multiple organ dysfunction,exacerbating the pathological progression of sepsis.This study focuses on the role of palmitoyltransferase ZDHHC18 in sepsis,proposing that it may regulate the formation of neutrophil NETs through palmitoylation,thereby promoting the onset of sepsis.Currently,there is no research,domestically or internationally,on the role of ZDHHC18 in NETs during sepsis.Therefore,exploring potential therapeutic strategies—such as inhibiting ZDHHC18 to mitigate the pathological effects of sepsis—could provide new insights for treating sepsis-related inflammatory diseases.
