Cardiovascular disease risk and pathogenesis in systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) often features extensive cardiovascular (CV) comorbidity and patients with SLE are at significantly increased risk of CV event occurrence and CV-related mortality. While the specific mechanisms leading to this increased cardiovascular disease (CVD) risk remain to be fully characterized, this heightened risk cannot be fully explained by traditional CV risk factors and is likely driven by immunologic and inflammatory features of SLE. Widespread innate and adaptive immune dysregulation characterize SLE, and factors including excessive type I interferon burden, inappropriate formation and ineffective clearance of neutrophil extracellular traps, and autoantibody formation have been linked to clinical and metabolic features impacting CV risk in SLE and may represent pathogenic drivers of SLE-related CVD. Indeed, functional and phenotypic aberrations in almost every immune cell type are present in SLE and may impact CVD progression. As understanding of the contribution of SLE-specific factors to CVD in SLE improves, improved screening and monitoring of CV risk alongside development of therapeutic treatments aimed at prevention of CVD in SLE patients are required and remain the focus of several ongoing studies and lines of inquiry.

Keywords: Atherosclerosis; Innate immunity; Systemic lupus erythematosus; Vascular biology.

Figure. 1

Traditional and SLE-specific CV risk factors. In addition to traditional risk factors for CVD, SLE-specific risk factors based in the immunologic and inflammatory characteristics of SLE likely play a role in the pathogenesis of SLE-related CVD. Created with BioRender.com

Figure. 2

Mechanisms potentially underlying CVD pathogenesis in SLE. Several SLE-specific factors influence vascular health by contributing to accelerated atherosclerosis and vascular damage. AAVEs, autoantibodies against vascular endothelial cadherin; anti-LPL, anti-lipoprotein lipase antibodies; aPL, antiphospholipid antibodies; endoMT, endothelial-mesenchymal transition, HDL, high-density lipoprotein; IFN-I, type I interferons; LDL, low-density lipoprotein; MMP, matrix metalloproteinase; NETs, neutrophil extracellular traps; oxHDL, oxidized high-density lipoprotein; oxLDL, oxidized low-density lipoprotein; pDC, plasmacytoid dendritic cell; VE-cadherin, vascular endothelial cadherin. Created with BioRender.com