Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jun;228(2):380-5.
doi: 10.1016/j.atherosclerosis.2013.03.029. Epub 2013 Apr 6.

Beyond LDL-C Lowering: Distinct Molecular Sphingolipids Are Good Indicators of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Deficiency

Affiliations
Free article

Beyond LDL-C Lowering: Distinct Molecular Sphingolipids Are Good Indicators of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Deficiency

Minna T Jänis et al. Atherosclerosis. .
Free article

Abstract

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.

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).

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.

Conclusions: Plasma molecular lipid species may be utilized for characterizing novel compounds inhibiting PCSK9 and as sensitive efficacy markers of the PCSK9 inhibition.

Similar articles

See all similar articles

Cited by 9 articles

See all "Cited by" articles

Publication types

LinkOut - more resources

Feedback