Matches in SemOpenAlex for { <https://semopenalex.org/work/W2783255589> ?p ?o ?g. }
Showing items 1 to 88 of
88
with 100 items per page.
- W2783255589 abstract "Introduction: Sirtuin 1 (SIRT1), an NAD + - dependent deacetylase enzyme is an important regulator of nutrient metabolism. Hepatic LDL receptor (LDL-R) expression confers atheroprotection by clearing cholesterol from blood. Previously, we have shown that SIRT1 activation protects against atherosclerosis through its effect on PCSK9 expression. However, the role of secreted SIRT1 in atherosclerosis is yet unknown. Hypothesis: Circulating SIRT1 protects against atherosclerosis through an increase in hepatic LDL-R expression and a decrease in plasma PCSK9 activity. Methods: Male ApoE -/- mice (n=6) on a high-cholesterol diet (1.25% w/w) were treated with recombinant SIRT1 (rSIRT1) or PBS (vehicle) for 10 weeks and were assessed for severity of aortic atherosclerosis, plasma lipids and hepatic protein expression. PCSK9 and SIRT1 expression was measured in healthy subjects of different age groups (n=80) and in hypercholesterolaemic patients (n=70) by ELISA. In vitro experiments were performed in Huh7 hepatoma cells. Results: Genetic overexpression of GFP-tagged SIRT1 confirms that SIRT1 is indeed secreted in Huh7 cells. Plasma SIRT1 levels decrease in an age-dependent manner in healthy subjects and inversely correlates with plasma LDL-C and PCSK9 in healthy subjects and hypercholestrolaemic patients. ApoE -/- mice treated with rSIRT1 showed less atherosclerosis and had lower levels of plasma cholesterol (LDL- and total cholesterol) compared vehicle-treated controls. Hepatic LDL-R protein expression increased with no change in LDL-R or PCSK9 mRNA levels. SIRT1 was found bound to PCSK9 immunoprecipitated from plasma of healthy subjects. Correspondingly, mass spectrometry revealed PCSK9 to have four acetylation sites which are deacetylated by SIRT1. In vitro, rSIRT1 increased LDL-R expression in a time-dependent manner in Huh7 cells. LDL-R-PCSK9 binding assay showed that deacetylated PCSK9 binds to a lower extent to LDL-R EGF-A domain compared to control PCSK9. Conclusion: SIRT1 secretion reduces with age. Pharmacological treatment with rSIRT1 protects against atherosclerosis through a decrease in LDL-C and an increase in LDL-R. Our findings demonstrate a link into why LDL-C increases as we age, causing an increase risk to atherosclerosis." @default.
- W2783255589 created "2018-01-26" @default.
- W2783255589 creator A5000296743 @default.
- W2783255589 creator A5000702424 @default.
- W2783255589 creator A5001127450 @default.
- W2783255589 creator A5036090523 @default.
- W2783255589 creator A5040218329 @default.
- W2783255589 creator A5040563213 @default.
- W2783255589 creator A5059525247 @default.
- W2783255589 creator A5088872496 @default.
- W2783255589 creator A5088905034 @default.
- W2783255589 date "2016-11-11" @default.
- W2783255589 modified "2023-10-09" @default.
- W2783255589 title "Abstract 19426: Circulating Sirt1 Protects Against Atherosclerosis Through Its Modulation of Pcsk9 Activity" @default.
- W2783255589 hasPublicationYear "2016" @default.
- W2783255589 type Work @default.
- W2783255589 sameAs 2783255589 @default.
- W2783255589 citedByCount "0" @default.
- W2783255589 crossrefType "journal-article" @default.
- W2783255589 hasAuthorship W2783255589A5000296743 @default.
- W2783255589 hasAuthorship W2783255589A5000702424 @default.
- W2783255589 hasAuthorship W2783255589A5001127450 @default.
- W2783255589 hasAuthorship W2783255589A5036090523 @default.
- W2783255589 hasAuthorship W2783255589A5040218329 @default.
- W2783255589 hasAuthorship W2783255589A5040563213 @default.
- W2783255589 hasAuthorship W2783255589A5059525247 @default.
- W2783255589 hasAuthorship W2783255589A5088872496 @default.
- W2783255589 hasAuthorship W2783255589A5088905034 @default.
- W2783255589 hasConcept C104317684 @default.
- W2783255589 hasConcept C126322002 @default.
- W2783255589 hasConcept C127561419 @default.
- W2783255589 hasConcept C134018914 @default.
- W2783255589 hasConcept C170493617 @default.
- W2783255589 hasConcept C181199279 @default.
- W2783255589 hasConcept C2776536020 @default.
- W2783255589 hasConcept C2778163477 @default.
- W2783255589 hasConcept C2780072125 @default.
- W2783255589 hasConcept C2780561631 @default.
- W2783255589 hasConcept C2780948078 @default.
- W2783255589 hasConcept C43554185 @default.
- W2783255589 hasConcept C55493867 @default.
- W2783255589 hasConcept C62746215 @default.
- W2783255589 hasConcept C71924100 @default.
- W2783255589 hasConcept C75520062 @default.
- W2783255589 hasConcept C86803240 @default.
- W2783255589 hasConceptScore W2783255589C104317684 @default.
- W2783255589 hasConceptScore W2783255589C126322002 @default.
- W2783255589 hasConceptScore W2783255589C127561419 @default.
- W2783255589 hasConceptScore W2783255589C134018914 @default.
- W2783255589 hasConceptScore W2783255589C170493617 @default.
- W2783255589 hasConceptScore W2783255589C181199279 @default.
- W2783255589 hasConceptScore W2783255589C2776536020 @default.
- W2783255589 hasConceptScore W2783255589C2778163477 @default.
- W2783255589 hasConceptScore W2783255589C2780072125 @default.
- W2783255589 hasConceptScore W2783255589C2780561631 @default.
- W2783255589 hasConceptScore W2783255589C2780948078 @default.
- W2783255589 hasConceptScore W2783255589C43554185 @default.
- W2783255589 hasConceptScore W2783255589C55493867 @default.
- W2783255589 hasConceptScore W2783255589C62746215 @default.
- W2783255589 hasConceptScore W2783255589C71924100 @default.
- W2783255589 hasConceptScore W2783255589C75520062 @default.
- W2783255589 hasConceptScore W2783255589C86803240 @default.
- W2783255589 hasOpenAccess W2783255589 @default.
- W2783255589 hasRelatedWork W1829579727 @default.
- W2783255589 hasRelatedWork W2018294076 @default.
- W2783255589 hasRelatedWork W2099136586 @default.
- W2783255589 hasRelatedWork W2131607570 @default.
- W2783255589 hasRelatedWork W2146238817 @default.
- W2783255589 hasRelatedWork W2151133405 @default.
- W2783255589 hasRelatedWork W2290054058 @default.
- W2783255589 hasRelatedWork W2301196075 @default.
- W2783255589 hasRelatedWork W2351184530 @default.
- W2783255589 hasRelatedWork W2574261439 @default.
- W2783255589 hasRelatedWork W2584348139 @default.
- W2783255589 hasRelatedWork W2589580491 @default.
- W2783255589 hasRelatedWork W2790540315 @default.
- W2783255589 hasRelatedWork W2895548902 @default.
- W2783255589 hasRelatedWork W2902930525 @default.
- W2783255589 hasRelatedWork W2903840607 @default.
- W2783255589 hasRelatedWork W2966658839 @default.
- W2783255589 hasRelatedWork W3145276534 @default.
- W2783255589 hasRelatedWork W3204943439 @default.
- W2783255589 hasRelatedWork W2553945205 @default.
- W2783255589 hasVolume "134" @default.
- W2783255589 isParatext "false" @default.
- W2783255589 isRetracted "false" @default.
- W2783255589 magId "2783255589" @default.
- W2783255589 workType "article" @default.