Beyond LDL-C lowering: Distinct molecular sphingolipids are good indicators of proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency

作者：Janis Minna T; Tarasov Kirill; Ta Hung Xuan; Suoniemi Matti; Ekroos Kim; Hurme Reini; Lehtimaki Terho; Paiva Hannu; Kleber Marcus E; Maerz Winfried; Prat Annik; Seidah Nabil G; Laaksonen Reijo^*

来源：Atherosclerosis, 2013, 228(2): 380-385.

DOI：10.1016/j.atherosclerosis.2013.03.029

• PCSK9
• Biomarker
• Lipidomics

Objectives: Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has been proposed to be a potential new therapeutic target for treatment of hypercholesterolaemia. However, little is known about the effects of PCSK9 inhibition on the lipidome. %26lt;br%26gt;Methods: We performed molecular lipidomic analyses of plasma samples obtained from PCSK9-deficient mice, and serum of human carriers of a loss-of-function variant in the PCSK9 gene (R46L). %26lt;br%26gt;Results: In both mouse and man, PCSK9 deficiency caused a decrease in several cholesteryl esters (CE) and short fatty acid chain containing sphingolipid species such as CE 16: 0, glucosyl/galactosylceramide (Glc/GalCer) d18:1/16:0, and lactosylceramide (LacCer) d18:1/16:0. In mice, the changes in lipid concentrations were most prominent when animals were given regular chow diet. In man, a number of molecular lipid species was shown to decrease significantly even when LDL-cholesterol was non-significantly reduced by 10% only. Western diet attenuated the lipid lowering potency of PCSK9 deficiency in mice. %26lt;br%26gt;Conclusions: Plasma molecular lipid species may be utilized for characterizing novel compounds inhibiting PCSK9 and as sensitive efficacy markers of the PCSK9 inhibition.

• 出版日期2013-6
• 单位河北医科大学