Plasma HDL pattern, cholesterol efflux and cholesterol loading capacity of serum in carriers of a novel missense variant (Gly176Trp) of endothelial lipase.
• Phenotypic description of family members with primary hyperalphalipoproteinemia. • Identification of a novel likely pathogenic variant of LIPG in three subjects. • Large HDL particles and reduced preβ-HDL content found in variant carriers. • Decreased ABCA1- and ABCG1-mediated cholesterol efflux c...
| Publicado en: | Journal of Clinical Lipidology Vol. 16; no. 5; pp. 694 - 704 |
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| Autores principales: | , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Elsevier B.V.
Sep2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=160168129&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 160168129 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 19332874 54Y0 jtl: Journal of Clinical Lipidology issn: 19332874 maglogo: N pubinfo: dt: Sep2022 vid: 16 iid: 5 pid: 467 pub: Elsevier B.V. place: New York, New York artinfo: ui: 160168129 160168129 160168129 10.1016/j.jacl.2022.08.002 160168129 ppf: 694 ppct: 10 formats: tig: atl: Plasma HDL pattern, cholesterol efflux and cholesterol loading capacity of serum in carriers of a novel missense variant (Gly176Trp) of endothelial lipase. aug: au: Pisciotta, Livia Ossoli, Alice Ronca, Annalisa Garuti, Anna Fresa, Raffaele Favari, Elda Calabresi, Laura Calandra, Sebastiano Bertolini, Stefano affil: Department of Internal Medicine, University of Genoa, Genoa, Italy sug: subj: Hyperlipoproteinemia Familial and Genetic Lipoproteins, HDL Blood Cholesterol Blood Lipase Endothelial Cells Phenotype Genotype Mutation Human Electrophoresis Macrophages Sequence Analysis Enzyme-Linked Immunosorbent Assay Apolipoproteins Blood Descriptive Statistics ab: • Phenotypic description of family members with primary hyperalphalipoproteinemia. • Identification of a novel likely pathogenic variant of LIPG in three subjects. • Large HDL particles and reduced preβ-HDL content found in variant carriers. • Decreased ABCA1- and ABCG1-mediated cholesterol efflux capacity of carriers' sera Increased cholesterol loading capacity of carriers' sera in human macrophages. Loss of function variants of LIPG gene encoding endothelial lipase (EL) are associated with primary hyperalphalipoproteinemia (HALP), a lipid disorder characterized by elevated plasma levels of high density lipoprotein cholesterol (HDL-C). Aim of the study was the phenotypic and genotypic characterization of a family with primary HALP. HDL subclasses distribution was determined by polyacrylamide gradient gel electrophoresis. Serum content of preβ-HDL was assessed by (2D)-electrophoresis. Cholesterol efflux capacity (CEC) of serum mediated by ABCA1, ABCG1 or SR-BI was assessed using cells expressing these proteins. Cholesterol loading capacity (CLC) of serum was assayed using cultured human macrophages. Next generation sequencing was used for DNA analysis. Plasma EL mass was determined by ELISA. Three family members had elevated plasma HDL-C, apoA-I and total phospholipids, as well as a reduced content of preβ-HDL. These subjects were heterozygous carriers of a novel variant of LIPG gene [c.526 G>T, p.(Gly176Trp)] found to be deleterious in silico. Plasma EL mass in carriers was lower than in controls. CEC of sera mediated by ABCA1 and ABCG1 transporters was substantially reduced in the carriers. This effect was maintained after correction for serum HDL concentration. The sera of carriers were found to have a higher CLC in cultured human macrophages than control sera. The novel p.(Gly176Trp) variant of endothelial lipase is associated with changes in HDL composition and subclass distribution as well as with functional changes affecting cholesterol efflux capacity of serum which suggest a defect in the early steps of revere cholesterol transport. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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