Methotrexate Decreases the Level of PCSK9-A Novel Indicator of the Risk of Proatherogenic Lipid Profile in Psoriasis. The Preliminary Data

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) exerts an important role in inflammatory processes, lipids homeostasis, and cardiometabolic disorders that are closely associated with psoriasis. The aim of the study was to analyze the clinical and diagnostic value of serum PCSK9 concentrations and their connections with disease severity, inflammation, metabolic syndrome, and impact of systemic therapies in psoriatic patients. The study enrolled thirty-five patients with active plaque-type psoriasis and eighteen healthy volunteers served as controls. Blood samples were obtained before and after 12 weeks of treatment with methotrexate or acitretin. Serum PCSK9 concentrations were measured by the ELISA (Enzyme-Linked Immunosorbent Assay) commercial kits. Morphological and biochemical parameters were assayed using routine laboratory techniques. Psoriatic patients showed significantly elevated levels of PCSK9 compared to controls (p < 0.01), mostly in patients with a mild and moderate course of psoriasis. PCSK9 concentrations correlated positively with BMI and triglyceride levels (p < 0.05). Interestingly, PCSK9 had a strong negative correlation with low-density lipoprotein levels and total cholesterol (p < 0.05). Three months of monotherapy with methotrexate significantly reduced PCSK9 level (p < 0.05), on the contrary, the acitretin group showed a further increase of PCSK9 levels (p < 0.05). PCSK9 seems to be a novel marker of psoriasis and a putative explanation of lipid disturbances, which are common in patients with psoriasis and are vital for the further developing of metabolic syndrome. Methotrexate should be considered as a treatment of choice in patients with an elevated PCSK9 concentration.

Keywords: PCSK9; acitretin; lipid metabolism; methotrexate; proprotein convertase subtilisin/kexin type 9; psoriasis.

Figure 1

Comparison between PCSK9 concentrations before and after treatment in psoriatic patients and controls. ** means statistical significance with p < 0.01 compared to Controls. PCSK9, proprotein convertase subtilisin/kexin type 9.

Figure 2

Comparison between PCSK9 concentrations depending on the psoriasis area and the severity index (PASI) before treatment and controls. */** means statistical significance with p < 0.05/0.01 respectively, compared to Controls.

Figure 3

Comparison of PCSK9 concentrations between controls and patients sub-groups divided on a base of BMI scoring before and after treatment. * means statistical significance with p < 0.05 compared to Controls. # means significance with p < 0.05 compared to BMI 1 and BMI 2 subgroups. ^ means statistical significance with p < 0.05 for BMI 3 before treatment vs the same group after treatment. BMI, body mass index.

Figure 4

Comparison between PCSK9 concentations before and after treatment with acitretin and methotrexate separetely in psoriatic patients and controls. **/*** means statistical significance with p < 0.01/0.0001 respectively compared to Controls. ## means statistical significance with p < 0.01 between acitretin after treatment compared to methotrexate after treatment. ^^ means statistical significance with p < 0.01 between methotrexate before treatment compared to methotrexate after treatment.

Figure 5

Comparison between PCSK9 concentrations depending on psoriasis area and severity index (PASI) after treatment and controls. */** means statistical significance with p < 0.05/0.01 respectively, compared to Controls.