title: Extracellular DNA and histones: double-edged swords in immunothrombosis.
abstract: The existence of extracellular DNA in human plasma, also known as cell-free DNA (cfDNA), was first described in the 1940s. In recent years, there has been a resurgence of interest in the functional significance of cfDNA, particularly in the context of neutrophil extracellular traps (NETs). cfDNA and histones are key components of NETs that aid in the host response to infection and inflammation. However, cfDNA and histones may also exert harmful effects by triggering coagulation, inflammation, and cell death and by impairing fibrinolysis. In this article, we will review the pathologic nature of cfDNA and histones in macrovascular and microvascular thrombosis, including venous thromboembolism, cancer, sepsis, and trauma. We will also discuss the prognostic value of cfDNA and histones in these disease states. Understanding the molecular and cellular pathways regulated by cfDNA and histones may provide novel insights to prevent pathological thrombus formation and vascular occlusion.
authors.affiliation: Department of Medical Sciences, McMaster University, Hamilton, ON, Canada.|Thrombosis and Atherosclerosis Research Institute (TaARI), McMaster University, Hamilton, ON, Canada.
authors.forename: T J
authors.initials: TJ
authors.lastname: Gould
authors.affiliation: Department of Medical Sciences, McMaster University, Hamilton, ON, Canada.|Thrombosis and Atherosclerosis Research Institute (TaARI), McMaster University, Hamilton, ON, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Lysov
authors.affiliation: Thrombosis and Atherosclerosis Research Institute (TaARI), McMaster University, Hamilton, ON, Canada.|Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: P C
authors.initials: PC
authors.lastname: Liaw
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D004247:DNA / Q000097:blood* / Q000276:immunology; D065206:Extracellular Traps / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006657:Histones / Q000097:blood* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000235:genetics / Q000276:immunology; D009369:Neoplasms / Q000097:blood / Q000235:genetics / Q000276:immunology; D011655:Pulmonary Embolism / Q000097:blood* / Q000235:genetics / Q000276:immunology; D018805:Sepsis / Q000097:blood / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013927:Thrombosis / Q000097:blood* / Q000235:genetics / Q000276:immunology; D054556:Venous Thromboembolism / Q000097:blood / Q000235:genetics / Q000276:immunology; D014947:Wounds and Injuries / Q000097:blood / Q000235:genetics / Q000276:immunology
chemical_list: D006657:Histones; D004247:DNA
keywords: DNA; histones; sepsis; thrombosis; trauma