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

Abstract

Background: 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.

Elevated circulating Krüppel-like factor 4 level as a novel independent marker of the proatherogenic risk in patients with psoriasis: a preliminary study

“…Psoriasis is a systemic disease closely related with CMDs mainly through metabolically-driven inflammation. Recent papers published by our team and others showed that psoriatics still require discoveries of new markers of the disease as well as underlying conditions related to the psoriatic progression [1,20]. KLFs have been an area of intense research lately and thus they constitute a huge excitement for their potential role in medicine, in multiple diseases, not only CVD, but also psoriasis.…”

Aberrations in Lipid Expression and Metabolism in Psoriasis

“…PCSK9 inhibitors act by inhibiting PCSK9 (proprotein convertase subtilisin/kexin type 9), which prevents the binding of PCSK9 with LDL receptors on hepatocytes and the loss of such receptors, resulting in upregulation of their number and a decrease in LDL blood concentration [ 58 ]. Our team of dermatologists has investigated PCSK9 serum concentration in psoriatic patients and discovered that PCSK9 levels are significantly elevated in such patients and may become a marker of cardiometabolic disorder risk in PSO [ 62 ].…”

PCSK9/LDLR System and Rheumatoid Arthritis-Related Atherosclerosis

“…Secondly, our RA patients were in remission or low disease activity; hence we could not evaluate an association between inflammation in RA, subclinical CVD and PCSK9 levels. Lastly, specific RA-related therapies were not included in the analysis, due to the small sample size, even if there are indications from recent publications that they could affect PCSK9 levels or even lipid profile in RA (33)(34)(35).…”