Mechanistic insight into premature atherosclerosis and cardiovascular complications in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is associated with a significant risk of cardiovascular disease (CVD), which substantially increases disease mortality and morbidity. The overall mechanisms associated with the development of premature atherosclerosis and CVD in SLE remain unclear, but has been considered as a result of an intricate interplay between the profound immune dysregulation and traditional CVD risk factors. Aberrant systemic inflammation in SLE may lead to an abnormal lipid profile and dysfunction, which can further fuel the pro-atherosclerotic environment. The existence of a strong imbalance between endothelial damage and vascular repair/angiogenesis promotes vascular injury, which is the early step in the progression of atherosclerotic CVD. Profound innate and adaptive immune dysregulation, characterized by excessive type I interferon burden, aberrant macrophage, platelet and complements activation, neutrophil dysregulation and neutrophil extracellular traps formation, uncontrolled T cell activation, and excessive autoantibody production and immune complex formation, have been proposed to promote accelerated CVD in SLE. While designing targeted therapies to correct the dysregulated immune activation may be beneficial in the treatment of SLE-related CVD, much additional work is needed to determine how to translate these findings into clinical practice. Additionally, a number of biomarkers display diagnostic potentials in improving CVD risk stratification in SLE, further prospective studies will help understand which biomarker(s) will be the most impactful one(s) in assessing SLE-linked CVD. Continued efforts to identify novel mechanisms and to establish criteria for assessing CVD risk as well as predicting CVD progression are in great need to improve CVD outcomes in SLE.