Proprotein convertase subtilisin/kexin type 9 is related to disease activity and damage in patients with systemic erythematosus lupus

Abstract

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation and that has been linked to cardiovascular (CV) disease. The purpose of the present study was to examine whether PCSK9 levels are disrupted compared with controls in patients with systemic lupus erythematosus (SLE). We additionally sought to establish whether PCSK9 is related to both the abnormalities in the lipid profile and to the disease activity or damage of patients with SLE. Methods: We performed a cross-sectional study that encompassed 366 individuals: 195 SLE patients and 171 age-, sex-, and statin intake-matched controls. PCSK9, lipoproteins serum concentrations, and lipid profiles were assessed in patients and controls. A multivariable analysis, adjusted for standard CV risk factors, was performed to evaluate the role of PCSK9 in SLE-related dyslipidemia. Results: Most lipid related-molecules were decreased in patients with SLE compared with controls. This downregulation included PCSK9, with PCSK9 levels being lower in patients than controls in the full multivariable analysis, including the modifications in lipid profiles that the disease itself produces {beta coefficient –73 [95% confidence interval (CI) –91 to –54] ng/ml, p ⩽ 0.001}. Both SLICC and SLEDAI scores were independently and positively related to PCSK9. Patients currently on hydroxychloroquine exhibited decreased levels of PCSK9 compared with those that were not taking hydroxychloroquine [beta coefficient –30 (95% CI −54 to −6) ng/ml, p = 0.015]. Conclusion: PCSK9 is downregulated in SLE compared with controls, but SLE patients with higher disease activity and damage exhibited higher PSCK9 serum levels.

Key Molecules of Triglycerides Pathway Metabolism Are Disturbed in Patients With Systemic Lupus Erythematosus

“…Patients with systemic lupus erythematosus (SLE) have a high prevalence of premature CVD ( 7 ). Besides, they exhibit changes in serum lipids and lipoproteins ( 8 , 9 ). Although studies have reported a variety of modifications of lipid metabolism in patients with SLE, this alteration appears to be characterized by low HDL cholesterol, high triglycerides, and normal or elevated LDL cholesterol ( 10 , 11 ).…”

Apolipoprotein C-III in patients with systemic lupus erythematosus

“…Systemic lupus erythematosus (SLE) has been associated with increased cardiovascular (CV) disease [ 1 ] and altered lipid profile [ 2 ]. Although the exact mechanisms by which this occurs are unknown, it is believed that the inflammation that accompanies the disease is responsible for dyslipidemia and the increased CV risk that occurs in patients with SLE [ 3 ].…”

Serum Levels of Lipoprotein Lipase Are Increased in Patients with Inflammatory Bowel Disease

“…There is ample evidence showing that chronic inflammation impairs and alters lipoprotein metabolism and causes a variety of changes in plasma lipid and lipoprotein concentrations. This has been widely described in diseases such as systemic lupus erythematosus [ 14 , 15 ] and rheumatoid arthritis [ 16 ]. In addition, LPL is known to be upregulated in patients with systemic lupus erythematosus [ 17 ].…”