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Structural determin...
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Del Giudice, RitaLund University,Lunds universitet,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,Medical Protein Science,Lund University Research Groups
(författare)
Structural determinants in ApoA-I amyloidogenic variants explain improved cholesterol metabolism despite low HDL levels
- Artikel/kapitelEngelska2017
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Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:9a8c916b-3cad-4b0d-9f9d-65ea8859893d
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https://lup.lub.lu.se/record/9a8c916b-3cad-4b0d-9f9d-65ea8859893dURI
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https://doi.org/10.1016/j.bbadis.2017.09.001DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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Twenty Apolipoprotein A-I (ApoA-I) variants are responsible for a systemic hereditary amyloidosis in which protein fibrils can accumulate in different organs, leading to their failure. Several ApoA-I amyloidogenic mutations are also associated with hypoalphalipoproteinemia, low ApoA-I and high-density lipoprotein (HDL)-cholesterol plasma levels; however, subjects affected by ApoA-I-related amyloidosis do not show a higher risk of cardiovascular diseases (CVD). The structural features, the lipid binding properties and the functionality of four ApoA-I amyloidogenic variants were therefore inspected in order to clarify the paradox observed in the clinical phenotype of the affected subjects. Our results show that ApoA-I amyloidogenic variants are characterized by a different oligomerization pattern and that the position of the mutation in the ApoA-I sequence affects the molecular structure of the formed HDL particles. Although lipidation increases ApoA-I proteins stability, all the amyloidogenic variants analyzed show a lower affinity for lipids, both in vitro and in ex vivo mouse serum. Interestingly, the lower efficiency at forming HDL particles is compensated by a higher efficiency at catalysing cholesterol efflux from macrophages. The decreased affinity of ApoA-I amyloidogenic variants for lipids, together with the increased efficiency in the cholesterol efflux process, could explain why, despite the unfavourable lipid profile, patients affected by ApoA-I related amyloidosis do not show a higher CVD risk.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Domingo-Espín, JoanLund University,Lunds universitet,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,Medical Protein Science,Lund University Research Groups(Swepub:lu)med-jdg
(författare)
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Iacobucci, IlariaUniversity of Naples Federico II
(författare)
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Nilsson, OktawiaLund University,Lunds universitet,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,Medical Protein Science,Lund University Research Groups(Swepub:lu)med-owi
(författare)
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Monti, Maria CristinaUniversity of Naples Federico II
(författare)
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Monti, Daria MariaUniversity of Naples Federico II
(författare)
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Lagerstedt, Jens OLund University,Lunds universitet,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,Medical Protein Science,Lund University Research Groups(Swepub:lu)med-jls
(författare)
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Medicinsk proteinvetenskapForskargrupper vid Lunds universitet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Biochimica et Biophysica Acta: Elsevier BV1863:12, s. 3038-30480006-3002
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Ingår i:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease: Elsevier BV1863:12, s. 3038-30480925-4439
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