Extracellular DNA and histones: double-edged swords in immunothrombosis

Area of Science:

• Biochemistry
• Immunology
• Pathology

Background:

• Cell-free DNA (cfDNA) in human plasma, known since the 1940s, is gaining attention for its role in neutrophil extracellular traps (NETs).
• cfDNA and histones are integral to NETs, contributing to host defense against pathogens.
• However, these molecules can also drive pathological processes like coagulation and inflammation.

Purpose of the Study:

• To review the pathological roles of cfDNA and histones in macrovascular and microvascular thrombosis.
• To discuss the prognostic significance of cfDNA and histones in various disease states.
• To explore potential therapeutic strategies targeting cfDNA and histones for preventing vascular occlusion.

Main Methods:

• Literature review of studies on cfDNA and histones in thrombosis.
• Analysis of cfDNA and histone involvement in conditions such as venous thromboembolism, cancer, sepsis, and trauma.
• Examination of molecular and cellular pathways linking cfDNA/histones to pathological thrombus formation.

Main Results:

• cfDNA and histones contribute to pathological thrombus formation and vascular occlusion.
• These molecules play a role in inflammation, coagulation, and impaired fibrinolysis.
• Elevated cfDNA and histone levels are associated with adverse outcomes in various diseases.

Conclusions:

• cfDNA and histones are key mediators of thrombosis and inflammation in multiple disease contexts.
• Their prognostic value highlights their importance in disease progression.
• Targeting cfDNA and histone pathways may offer novel therapeutic avenues for thrombotic disorders.