부산대학교 도서관

Introduction: Psoriasis is a chronic inflammatory disease associated with increased levels of activated neutrophils, lower cholesterol efflux capacity (CEC), and subclinical atherosclerosis. High-density lipoprotein cholesterol efflux is the primary method of cholesterol removal from peripheral tissues and is linked to innate immunity and cardiovascular disease. Preclinical models suggest a strong relationship between CEC, neutrophil frequency and activation, and atherosclerosis, yet this relationship is understudied in clinical models.Hypothesis: (1) Psoriasis patients with high neutrophils have lower CEC and high non-calcified coronary burden (NCB); (2) CEC mediates the relationship between neutrophils and NCB.Methods: Coronary computed tomography angiography was used to quantitate NCB in one-hundred seventy-nine untreated psoriasis patients. Circulating neutrophils were measured via flow cytometry, and mean fluorescence intensity of CD62L and CD11b was determined. CEC was quantified using a cell-based ex-vivo assay measuring the ability of apolipoprotein B depleted plasma to mobilize cholesterol from lipid-loaded macrophages.Results: Patients with high neutrophils had decreased CEC (0.93 (0.15) vs 1.00 (0.17); P=0.03) and higher NCB (1.24 (0.55) vs 1.10 (0.50); P=0.003). The relationship between neutrophils and NCB was mediated by CEC beyond adjustment for Framingham risk score, smoking status, and statin treatment (20%, P=<0.001) (Figure 1). CEC associated with neutrophil activation markers, CD11b and CD62L (β: -0.23 P=0.04, β:0.21, P=0.04). Finally, one year of biologic therapy improved CEC (0.08 (0.17) vs (-0.009 (0.19); P=0.008) and neutrophil counts (-0.45 (-1.36- -0.45) vs -0.14 (-0.60-0.42; P=0.004).Conclusion: Patients with more neutrophils had lower CEC and higher NCB. Further, CEC mediates the relationship between neutrophils and NCB, underscoring the relationship between neutrophils and CEC in atherosclerosis.