Integrated multi-omics profiling reveals neutrophil extracellular traps potentiate Aortic dissection progression

Area of Science:

• Cardiovascular Biology
• Immunology
• Genomics

Background:

• Adverse aortic remodeling post-thoracic endovascular aortic repair (TEVAR) for aortic dissection (AD) increases adverse events (AAEs).
• Identifying prognostic indicators and therapeutic targets is crucial for optimizing TEVAR efficacy in AD patients.

Purpose of the Study:

• To investigate the molecular mechanisms underlying adverse aortic remodeling in AD.
• To identify novel biomarkers for predicting AAEs after TEVAR in AD patients.

Main Methods:

• Proteomic and single-cell transcriptomic analyses of peripheral blood and aortic lesions from AD patients and healthy controls.
• In vivo studies using mouse models of aortic dissection to assess the therapeutic potential of targeting NETs formation.

Main Results:

• Highly phenotype-associated macrophages orchestrate neutrophil extracellular traps (NETs) via the CXCL3/CXCR2 axis, promoting AD development.
• Increased NETs formation is a hallmark of systemic immunity and the aortic microenvironment in AD.
• Inhibition of NETs formation ameliorates AD progression and rupture in mice.
• Plasma citrullinated histone H3 levels predict AAEs following endovascular therapy.

Conclusions:

• NETs, orchestrated by macrophages through the CXCL3/CXCR2 axis, are key drivers of AD progression.
• Targeting NETs formation offers a potential therapeutic strategy for AD.
• Plasma citrullinated histone H3 serves as a valuable biomarker for risk stratification and prognostic evaluation in AD patients undergoing endovascular repair.