Abstract 14905: Association of Neutrophils and Neutrophil Extracellular Traps With Aortic Vascular Inflammation in Psoriasis.

Introduction: Cardiovascular disease (CVD) risk is increased in psoriasis, a chronic inflammatory disease that affects 2-3% of the population. Notably, psoriasis is associated with increased aortic vascular inflammation (VI) compared to non-psoriasis. Recently, neutrophils and associated neutrophil extracellular traps (NETs) have gained attention in inflammatory atherogenesis in pre-clinical models. Hypothesis: Neutrophils and NETs proteins would associate with aortic vascular inflammation. Methods: Consecutively recruited psoriasis patients (N=81) and healthy controls (n=36) underwent FDG PET/CT for assessment of VI (global aorta) as target-to-background ratio. Circulating neutrophils were measured via flow cytometry. Circulating NETs and deoxyribose nuclease 1 (DNase 1) levels were measured by ELISA. In vitro experiments were conducted to investigate NET-induced changes in Human Aortic Endothelial Cell (HAoEC) gene expression. Results: Neutrophil frequency was increased in psoriasis (p=0.01) compared to non-psoriasis and associated with aortic vascular inflammation beyond CVD risk factors (β=0.27, p=0.04). Psoriasis was associated with increased circulating NETs (Histone 4-associated NET absorbance p=0.056) and decreased NET clearance (DNase 1 concentration; p<0.0001). Finally, human aortic endothelial cells (HAoECs) co-cultured with psoriasis NETs had upregulated expression of ICAM-1, VCAM-1, and E-Selectin (p<0.05). Conclusions: Aortic vascular inflammation in psoriasis was associated with neutrophil frequency. Psoriasis was associated with poor clearance of elevated circulating NETs and neutrophil NETs activated endothelial cells. These data suggest that psoriasis neutrophils produce NETs which may adhere to and damage the endothelium augmenting aortic vascular inflammation. [ABSTRACT FROM AUTHOR]