Exploring novel markers for coronary heart disease associated with systemic lupus erythematosus: A review

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune condition that is characterized by the production of autoantibodies and sustained inflammatory damage. Coronary heart disease (CHD) is a common complication of SLE, significantly increases CHD-related mortality in SLE patients. Despite conventional risk factors, the mechanisms contributing to a higher CHD risk require further investigation, with the immune and inflammatory aspects of SLE playing a significant role. Endothelial cell damage and dysfunction are key factors in the progression of coronary atherosclerosis in SLE patients. This review specifically focuses on endothelial dysfunction and the role of specific microRNAs in the context of SLE and CHD. In addition, we discuss the effects and functions of oxidative stress markers, endothelial progenitor cells, and circulating endothelial cells in individuals with both SLE and CHD. We also explored the typical inflammatory markers associated with SLE and CHD, addressing their clinical significance and limitations.

Figure 1.

Endothelial cells, chronic inflammation, and oxidative stress promote SLE complicated with CHD. Autoantibodies, chronic inflammation, and oxidative stress in SLE patients act on endothelial cells, damaging endothelial cells, and promoting endothelial dysfunction. The changes of biomarkers related to endothelial cells, chronic inflammation, and oxidative stress reflect their participation, which together promote SLE complicated with CHD. CHD = coronary heart disease, SLE = systemic lupus erythematosus.

Figure 2.

Mechanism of oxidative stress and inflammatory response leading to CHD associated with SLE. In the state of oxidative stress, the dysregulation of peroxide isoprostaglandins, MDA-LDL and antioxidant SOD promote the occurrence of atherosclerosis. In the inflammatory environment, macrophages produce PTX3 when stimulated by LPS, IL-1, and TNF-α. PTX3 co-promotes the occurrence of atherosclerosis with TNF-α/NF-κB. Under the stimulation of LPS and TNF-α, SuPAR can bind to αvβ3 integrins and promote atherosclerosis through NF-κB pathway. When the body is in inflammatory response, the expression of Galectin-3 is increased, which can accelerate the process of atherosclerosis through the NF-κB pathway or the PI3K pathway after binding with CD98. IL-1 = interleukin-1, LPS = lipopolysaccharide, MDA-LDL = malondialdehyde-modified low-density lipoprotein, NF-Κb = nuclear factor kappa-B, PI3K = phosphatidylinositol 3-kinase, PTX3 = pentatoxin-3, SOD = superoxide dismutase, SuPAR = soluble urokinase-type plasminogen activator receptor, TNF-α = tumor necrosis factor-α.

Figure 3.

The initiation and activation of inflammasome of NLRP3, and the production process of IFN-I. Specific PRRS (such as LPS, IL-1, and TNF-α) activate the NF-κB signaling pathway by recognizing PAMPs, and the body’s own DNA or RNA by recognizing DAMPs. Activation of NF-κB signaling causes NLRP3, pro-IL-1β, and pro-IL-18 to upregulate and activate NLRP3 inflammasome assembly, recruiting and activating pro-caspase-1. Activated caspase-1 cleaves the pro-inflammatory cytokines pro-IL-1β and pro-IL-18 into mature IL-1β and IL-18. RNA or DNA can also turn on the downstream MyD88, which increases the expression of IRF-3 and IRF-7 leading to IFN-I production, and IFN-1 prompts macrophages to become foam cells. DAMPs = damage-associated molecular patterns, IFN-I = type I interferon, IL-1β = interleukin-1β, IL-18 = interleukin-18, IL-1 = interleukin-1, IRF-3 = interferon regulatory factors-3, IRF-7 = interferon regulatory factors-7, LPS = lipopolysaccharide, MyD88 = myeloid differentiation factor 88, NF-Κb = nuclear factor kappa-B, NLRP3 = NLR family Pyrin domain-containing protein 3, PAMPs = pathogen-associated molecular patterns, PRRS = pattern recognition receptors, Pro-IL-1β = pro-interleukin-1β, Pro-IL-18 = pro-interleukin-18, TNF-α = tumor necrosis factor-α.