D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

Sophie Valleix (), Guglielmo Verona, Noémie Jourde-Chiche, Brigitte Nédelec, P. Patrizia Mangione, Frank Bridoux, Alain Mangé, Ahmet Dogan, Jean-Michel Goujon, Marie Lhomme, Carolane Dauteuille, Michèle Chabert, Riccardo Porcari, Christopher A. Waudby, Annalisa Relini, Philippa J. Talmud, Oleg Kovrov, Gunilla Olivecrona, Monica Stoppini, John Christodoulou, Philip N. Hawkins, Gilles Grateau, Marc Delpech, Anatol Kontush, Julian D. Gillmore, Athina D. Kalopissis and Vittorio Bellotti ()
Additional contact information
Sophie Valleix: Université Paris-Descartes, Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris, Laboratoire de Biologie et Génétique Moléculaire, Hôpital Cochin
Guglielmo Verona: Centre for Amyloidosis and Acute Phase Proteins, National Amyloidosis Centre, University College London
Noémie Jourde-Chiche: Université de Marseille, AP-HM, Hôpital de la Conception
Brigitte Nédelec: INSERM, UMR_1163, Institut Imagine, Laboratoire de Génétique Ophtalmologique (LGO), Université Paris Descartes, Sorbonne Paris Cité
P. Patrizia Mangione: Centre for Amyloidosis and Acute Phase Proteins, National Amyloidosis Centre, University College London
Frank Bridoux: Université de Poitiers, CHU Poitiers, Centre National de Référence Amylose AL et autres maladies par dépôts d'immunoglobulines monoclonales
Alain Mangé: Institut de Recherche en Cancérologie de Montpellier (IRCM)
Ahmet Dogan: Mayo Clinic
Jean-Michel Goujon: Université de Poitiers, CHU Poitiers, Service d’Anatomie et Cytologie Pathologiques, Centre National de Référence Amylose AL et autres maladies par dépôts d'immunoglobulines monoclonales
Marie Lhomme: Lipidomic core, ICANalytics, Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpôtrière Hospital
Carolane Dauteuille: Sorbonne Universités, UPMC Univ Paris 06, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S 1166, Hôpital de la Pitié
Michèle Chabert: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Université Paris-Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers
Riccardo Porcari: Centre for Amyloidosis and Acute Phase Proteins, National Amyloidosis Centre, University College London
Christopher A. Waudby: Institute of Structural and Molecular Biology, University College London and Birkbeck College, University of London
Annalisa Relini: University of Genoa
Philippa J. Talmud: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London
Oleg Kovrov: Umeå University
Gunilla Olivecrona: Umeå University
Monica Stoppini: Institute of Biochemistry, University of Pavia
John Christodoulou: Institute of Structural and Molecular Biology, University College London and Birkbeck College, University of London
Philip N. Hawkins: Centre for Amyloidosis and Acute Phase Proteins, National Amyloidosis Centre, University College London
Gilles Grateau: Hôpital Tenon, AP-HP, Service de Médecine Interne, Centre de référence des amyloses d'origine inflammatoire et de la fièvre méditerranéenne familiale
Marc Delpech: Université Paris-Descartes, Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris, Laboratoire de Biologie et Génétique Moléculaire, Hôpital Cochin
Anatol Kontush: Sorbonne Universités, UPMC Univ Paris 06, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S 1166, Hôpital de la Pitié
Julian D. Gillmore: Centre for Amyloidosis and Acute Phase Proteins, National Amyloidosis Centre, University College London
Athina D. Kalopissis: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Université Paris-Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers
Vittorio Bellotti: Centre for Amyloidosis and Acute Phase Proteins, National Amyloidosis Centre, University College London

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms10353 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10353

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10353

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().