Novel Insights in Systemic Lupus Erythematosus and Atherosclerosis

Abstract

IntroductionThe systemic inflammatory nature of systemic lupus erythematosus (SLE) is well patent not only in the diverse clinical manifestations of the disease but also in the increased risk of premature atherosclerosis and cardiovascular events (CVE), making SLE one of the most complex diseases to study and manage in clinical practice.AimTo travel from old aspects to modern insights on the physiopathology, new molecular biomarkers, imaging methods of atherosclerosis assessment, and the potential treatments of atherosclerosis in SLE.MethodsWe conducted a literature search using PubMed database and performed a critical review.Conclusion/discussionSeveral developments have taken place in the understanding of the relationship between SLE and premature atherosclerosis. Nevertheless, cardiovascular diseases are still the major cause of reduced life expectancy in SLE and the main cause of death. The lack of standardization methods for the imaging assessment of atherosclerosis in SLE and the multifactorial nature of the disease are well patriated in the difficulty of achieving consistent and reproducible results among studies that focus in cardiovascular risk assessment and prediction. A raising number of molecular biomarkers of atherosclerosis have been proposed, but the combination of several biomarkers and risk factors may better estimate cardiovascular disease risk. Moreover, the development of effective therapies to prevent progression of atherosclerosis and CVE shall address systemic inflammation.

Serum osteopontin negatively impacts on intima‐media thickness in patients with systemic lupus erythematosus

“…6,7 To estimate subclinical atherosclerosis, different non-invasive approaches have been used, including carotid intima-media thickness (cIMT), pulse wave velocity and myocardial perfusion strategies. 8 Among those approaches, ultrasound evaluation of cIMT is one of the most used for risk stratification in SLE patients, being characterized by a high sensitivity 9 and with a high predictive value for adverse CV events. 10,11 Conversely, the majority of biomarkers are burdened by low predictive value.…”

Role of the eNOS Uncoupling and the Nitric Oxide Metabolic Pathway in the Pathogenesis of Autoimmune Rheumatic Diseases

“…Therefore, precocious atherosclerosis is likely attributable to the consequences of inflammation, which is in line with observations that disease duration, higher damage index score, and less aggressive immunosuppression are associated with increased CVD burden in SLE patients. Till now, there are no biomarkers that predict CV events in SLE patients, and the known ones used to assess CV risk in the general population have limited or no value in SLE [143][144][145]. However, patients with SLE show enhanced endothelial dysfunction, which is regarded as a common mechanism for various CV disorders and considered the first step in atherosclerosis.…”

Type-I interferons in atherosclerosis

“…3;Goossens et al, 2010;Nakano et al, 2012). While the function of neutrophils in atherosclerosis is not completely clear (Drechsler et al, 2010), over recent years, emerging evidence has revealed the contributory role of neutrophils in atherogenesis and plaque instability (Teixeira and Tam, 2018). As a phagocytic granulocyte, neutrophils are capable of discharging granule proteins, proteases, and reactive oxygen species (ROS) and producing neutrophil extracellular traps (NETs; Döring et al, 2017).…”