Beyond LDL-C lowering: distinct molecular sphingolipids are good indicators of proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency.
Atherosclerosis
; 228(2): 380-5, 2013 Jun.
Article
em En
| MEDLINE
| ID: mdl-23623011
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 160, glucosyl/galactosylceramide (Glc/GalCer) d181/160, and lactosylceramide (LacCer) d181/160. 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esfingolipídeos
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Serina Endopeptidases
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Pró-Proteína Convertases
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LDL-Colesterol
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article