Imbalance between endothelial damage and repair: a gateway to cardiovascular disease in systemic lupus erythematosus.

Atherosclerosis is accelerated in patients with systemic lupus erythematosus (SLE) and it leads to excessive cardiovascular complications in these patients. Despite the improved awareness of cardiovascular disease and advent of clinical diagnostics, the process of atherogenesis in most patients remains clinically silent until symptoms and signs of cardiovascular complications develop. As evidence has demonstrated that vascular damage is already occurring before clinically overt cardiovascular disease develops in lupus patients, intervention at the preclinical stage of atherogenesis would be plausible. Indeed, endothelial dysfunction, one of the earliest steps of atherogenesis, has been demonstrated to occur in lupus patients even when they are naïve for cardiovascular disease. Currently known "endothelium-toxic" factors including type 1 interferon, proinflammatory cytokines, inflammatory cells, immune complexes, costimulatory molecules, neutrophils extracellular traps, lupus-related autoantibodies, oxidative stress, and dyslipidemia, coupled with the aberrant functions of the endothelial progenitor cells (EPC) which are crucial to vascular repair, likely tip the balance towards endothelial dysfunction and propensity to develop cardiovascular disease in lupus patients. In this review, altered physiology of the endothelium, factors leading to perturbed vascular repair contributed by lupus EPC and the impact of proatherogenic factors on the endothelium which potentially lead to atherosclerosis in lupus patients will be discussed.