Background Proteinase K-like serine protease PCSK9 binds the low-density lipoprotein (LDL) receptor at the surface of hepatocytes, thereby preventing its recycling and enhancing its degradation in endosomes/lysosomes, resulting in reduced LDL-cholesterol clearance. Therefore, gain-of-function in PCSK9 lead to higher levels of LDL-cholesterol and increased risk of cardiovascular disease.
Objectives To investigate how PCSK9, one of the molecules involved in the metabolism of LDL-cholesterol, is expressed in patients with rheumatoid arthritis (RA) and its potential relationship with the altered lipid profile observed in these patients.
Methods Plasma PCSK9 concentrations were measured in 115 patients with RA and 101 matched controls. A multivariable analysis adjusted for glucocorticoid intake, standard cardiovascular risk factors, disease activity and lipids, including LDL cholesterol, was performed to evaluate the relation of PCSK9 with RA dyslipidemia compared to controls.
Results Glucocorticoids-naïve RA patients showed lower levels of total cholesterol (216±39 vs 196±37 mg/dl, p=0.00), LDL cholesterol (135±36 vs 115±34 mg/dl, p=0.02), non-HDL cholesterol (161±40 vs 141±41 mg/dl, p=0.04) and apolipoproteins A1 (176±30 vs 162±32 mg/dl, p=0.01) and B (91±17 vs 82±18 mg/dl, p=0.00), compared to the control population. These differences were not found when control population was compared to patients treated with glucocorticoids. Resistin leves were higher in patients with RA (5.51±3.10 vs 6.27 [4.54-9.42], p=0.00), independently of glucocorticoid use. Conversely, while patients treated with corticosteroids showed no difference in PCSK9 levels compared to controls, these were significantly lower in glucocorticoids-naïve patients than controls (2.68±1.46 vs 2.22±1.18 μg/ml, p=0.03). LDL:HDL ratio cholesterol was not related with PCSK9 levels in RA patients or controls. PCSK9 levels showed no relation with parameters of activity or inflammation related to the disease.
Conclusions PCSK9 is down regulated in glucocorticoids-naïve RA patients.This is independent of the decrease in LDL cholesterol that the disease expresses.
Disclosure of Interest None declared