Changes in PCSK9 and LDL cholesterol concentrations by everolimus treatment and their effects on polymorphisms in PCSK9 and mTORC1.
Everolimus
Low-density lipoprotein cholesterol
Mammalian target of rapamycin complex 1
Polymorphism
Proprotein convertase subtilisin/kexin type 9
Journal
Pharmacological reports : PR
ISSN: 2299-5684
Titre abrégé: Pharmacol Rep
Pays: Switzerland
ID NLM: 101234999
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
09
09
2019
accepted:
20
02
2020
revised:
17
02
2020
pubmed:
28
3
2020
medline:
13
4
2021
entrez:
28
3
2020
Statut:
ppublish
Résumé
The purpose of this study was to evaluate the effects of concentrations of proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein (LDL) cholesterol by the mammalian target of rapamycin (mTOR) inhibitor everolimus and their effects on genetic polymorphisms in the PCSK9 and mTORC1 genes in 53 renal transplant recipients. Prior to and on day 15 after everolimus administration, the concentrations of everolimus in blood and PCSK9 and LDL cholesterol in plasma were evaluated. Additionally, mTORC1 (rs2536T>C and rs2295080T>G) and PCSK9 (rs505151G>A, rs562556G>A, and rs11593680C>T) polymorphisms were analyzed. Mean PCSK9 plasma concentrations on day 15 after everolimus treatment were significantly higher than those before treatment (295 versus 214 ng/mL, respectively; p = 0.004). Significant correlations between the area under the blood concentration-time curves (AUC) Administration of everolimus significantly elevated plasma PCSK9 concentrations, potentially causing everolimus-induced hyperlipidemia.
Sections du résumé
BACKGROUND
BACKGROUND
The purpose of this study was to evaluate the effects of concentrations of proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein (LDL) cholesterol by the mammalian target of rapamycin (mTOR) inhibitor everolimus and their effects on genetic polymorphisms in the PCSK9 and mTORC1 genes in 53 renal transplant recipients.
METHODS
METHODS
Prior to and on day 15 after everolimus administration, the concentrations of everolimus in blood and PCSK9 and LDL cholesterol in plasma were evaluated. Additionally, mTORC1 (rs2536T>C and rs2295080T>G) and PCSK9 (rs505151G>A, rs562556G>A, and rs11593680C>T) polymorphisms were analyzed.
RESULTS
RESULTS
Mean PCSK9 plasma concentrations on day 15 after everolimus treatment were significantly higher than those before treatment (295 versus 214 ng/mL, respectively; p = 0.004). Significant correlations between the area under the blood concentration-time curves (AUC)
CONCLUSIONS
CONCLUSIONS
Administration of everolimus significantly elevated plasma PCSK9 concentrations, potentially causing everolimus-induced hyperlipidemia.
Identifiants
pubmed: 32215854
doi: 10.1007/s43440-020-00090-6
pii: 10.1007/s43440-020-00090-6
doi:
Substances chimiques
Cholesterol, LDL
0
Everolimus
9HW64Q8G6G
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
622-630Références
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