Nickel exposure aggravates aortic dissection by exacerbating neutrophil recruitment and NETosis to compromise endothelial barrier.

Nickel exposure elevates aortic dissection (AD) risk, yet its pathogenic mechanisms remain unclear. Here, we demonstrate that nickel accelerates AD progression, particularly in hypertensive individuals. Bioinformatics analysis of GEO datasets identified chemokine-mediated endothelial-neutrophil crosstalk as a key pathway. Using a neutrophil-endothelial co-culture model, nickel activated the CXCL6/CXCL8-CXCR2 axis, triggering endothelial secretion of CXCL6/8 and upregulating neutrophil CXCR2 expression. This dual effect promoted neutrophil recruitment, adhesion, and migration, validated in nickel-exposed AD model mice and a case-control study. Nickel further induced neutrophil extracellular traps (NETs) formation via myeloperoxidase (MPO) and Citrullinated Histone H3 (CitH3) activation, compromising endothelial integrity through decreased Occludin/ZO-1 protein levels. Our findings reveal nickel-driven AD pathogenesis involves: CXCL6/8-CXCR2-mediated neutrophil recruitment, and NETosis-induced endothelial barrier disruption. This mechanistically links environmental nickel exposure to AD progression via neutrophil-endothelial dysregulation, providing critical insights for mitigating heavy metal-associated cardiovascular hazards.