Soluble LOX-1: A Potential biomarker for SLE and Cardiovascular Comorbidity

Abstract Cardiovascular disease is the leading cause of mortality among systemic lupus erythematosus (SLE) patients. LOX-1 is a scavenger receptor strongly implicated in plaque formation, progression and destabilization. It gets upregulated during vascular inflammation on endothelial cells, monocytes, macrophages, smooth muscle cells and platelets. Soluble LOX-1 (sLOX-1) can serve as a potential biomarker for identifying SLE patients with increased cardiovascular risk. In a 120 SLE patient cohort, circulating sLOX-1 levels were 2-fold higher compared to healthy controls, particularly in those14–40 years of age. Patients with high sLOX-1 had elevated proinflammatory HDL, oxLDL, CRP and SAA levels; known markers for vascular injury. High sLOX-1 patient HDL had higher cholesterol content and lower efflux capacity compared to healthy and low sLOX-1 HDL. Both patient derived monocytes and low-density granulocytes (LDGs) express significant levels of membrane LOX-1 compared to controls. Monocytes when conditioned with oxLDL and stimulated with immune complexes, release significant levels of sLOX-1 and cytokines through the LOX-1 receptor. SLE HDL failed to nuclear colocalize the inflammation resolution factor ATF3, in monocyte derived macrophages. Additionally, patient LDGs underwent rapid NETosis in the presence of immune complexes when primed with oxLDL, through the LOX-1 receptor. Disease modified lipoproteins in SLE function as LOX-1 ligand contributing to inflammatory immune activation adding to cardiovascular risk. Hence, sLOX-1 can be predictive of increased cardiovascular risk and LOX-1 receptor blockade may be a promising target for ameliorating cardiovascular damage in SLE.