Vascular damage in systemic lupus erythematosus

Vascular disease is a major cause of morbidity and mortality in patients with systemic autoimmune diseases, particularly systemic lupus erythematosus (SLE). Although comorbid cardiovascular risk factors are frequently present in patients with SLE, they do not explain the high burden of premature vascular disease. Profound innate and adaptive immune dysregulation seems to be the primary driver of accelerated vascular damage in SLE. In particular, evidence suggests that dysregulation of type 1 interferon (IFN-I) and aberrant neutrophils have key roles in the pathogenesis of vascular damage. IFN-I promotes endothelial dysfunction directly via effects on endothelial cells and indirectly via priming of immune cells that contribute to vascular damage. SLE neutrophils are vasculopathic in part because of their increased ability to form immunostimulatory neutrophil extracellular traps. Despite improvements in clinical care, cardiovascular disease remains the leading cause of mortality among patients with SLE, and treatments that improve vascular outcomes are urgently needed. Improved understanding of the mechanisms of vascular injury in inflammatory conditions such as SLE could also have implications for common cardiovascular diseases, such as atherosclerosis and hypertension, and may ultimately lead to personalized therapeutic approaches to the prevention and treatment of this potentially fatal complication. Here, the authors review traditional and disease-specific risk factors for vascular damage and the cellular and molecular mechanisms that drive vascular injury in systemic lupus erythematosus. They also discuss cardiovascular risk assessment, primary prevention strategies and current and future treatment approaches to cardiovascular disease in systemic lupus erythematosus. Systemic lupus erythematosus (SLE) is associated with an increased risk of developing cardiovascular disease (CVD), which is a leading cause of morbidity and mortality.Traditional risk factors, such as older age, male sex, smoking, hypertension, total cholesterol levels and diabetes mellitus, do not fully account for the increased risk of CVD among patients with SLE.Type 1 interferon and neutrophils may have important pathogenic roles in vascular damage in SLE.SLE remains a leading cause of premature death in women, mainly as a result of CVD; therefore, treatments that improve vascular outcomes are urgently needed.