Pediatric-onset systemic lupus erythematosus (pSLE) carries a high risk of premature cardiovascular disease, but responsive surrogate measures of cardiovascular risk for pediatric patients are currently lacking. Neutrophil extracellular traps (NETs) have recently been implicated in the pathogenesis of both SLE and atherosclerosis via endothelial activation in vitro, however nothing is known about NET-mediated endothelial injury and dysfunction in children and adolescents with pSLE. Endothelial dysfunction precedes structural changes in the continuum of atherosclerosis and may be a more sensitive, early indicator of vascular injury. This project is a longitudinal study of adolescents with pSLE recruited to undergo measurement of plasma NET levels and comprehensive vascular testing, including peripheral endothelial function testing and ambulatory blood pressure monitoring to assess nocturnal blood pressure decline, a potential surrogate marker of endothelial function. The objectives of this proposal are to: 1) determine the effect of pSLE and clinical disease activity measures on plasma NET levels, 2) determine the in vivo relationship between NET levels, markers of endothelial activation, and peripheral endothelial function in pSLE, and 3) determine whether NBP decline, a novel surrogate marker of atherosclerotic risk, is independently associated with peripheral endothelial function and structural evidence of subclinical atherosclerosis in adolescents with pSLE. The long-term goal is to understand mechanisms of vascular injury in pSLE and identify clinically useful biomarkers for earlier, more effective CV risk stratification and outcome assessment. The proposed research will contribute to our understanding of immunologic mechanisms of vascular injury and dysfunction in SLE, and apply novel, non-invasive approaches to cardiovascular assessment in children and adolescents with SLE.