Elevation of serum proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations and its possible atherogenic role in patients with systemic lupus erythematosus

Background: Systemic lupus erythematosus (SLE) patients have tendencies of accelerated atherosclerosis (AS) which can only partly be explained by traditional cardiovascular disease (CVD) risk factors. Imbalanced inflammation also plays a vital role. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new therapeutic target for AS for its dual mechanisms in lipids and inflammation. We aimed to assess serum PCSK9 concentrations in SLE patients and its possible role in atherogenesis of SLE. Methods: Ninety SLE patients and 50 healthy controls were included. SLE patients were further divided into SLE-AS and SLE-NonAS subgroups, according to the carotid intima-media thickness (cIMT). Traditional CVD risk factors, inflammatory biomarkers and PCSK9 concentrations were compared between: (I) SLE patients and controls; (II) SLE-AS subgroup and SLE-NonAS subgroup; (III) SLE patients with and without lupus nephritis (LN). Correlational analysis, univariate and multivariate linear regression analysis were applied to analyze the association between PCSK9 levels and disease parameter in SLE patients. Effects on PCSK9 concentrations by monotherapy with hydroxychloroquine (HCQ), which is thought having protective effects against AS in SLE, were investigated by follow-up analysis in 15 SLE patients. Results: We found that SLE patients had significantly elevated serum PCSK9 levels than controls, especially in SLE-As subgroup or those with LN, accompanied with higher ratio of cIMT thickening. Correlational analysis showed PCSK9 concentrations correlated with C-reactive protein (CRP) levels, age and erythrocyte sedimentation rate (ESR). Univariate and multivariate linear regression revealed that only CRP, but not age or ESR was positive predictors of PCSK9. Interestingly, monotherapy with HCQ for three months significantly reduced PCSK9 and CRP levels in inactive SLE patients. Conclusions: Our results suggested that elevated PCSK9 levels in SLE are probably associated with atherogenic inflammation in SLE. HCQ, which is thought having protective effects against AS in SLE, can effectively reduce PCSK9 levels in SLE patients.