| Added by | mollevi |
|---|---|
| Last modified by | alainmange |
| Group name | PlateformePP2I |
| Item Type | Journal Article |
| Title | D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile |
| Creator | Valleix et al. |
| Author | Sophie Valleix |
| Author | Guglielmo Verona |
| Author | Noémie Jourde-Chiche |
| Author | Brigitte Nédelec |
| Author | P. Patrizia Mangione |
| Author | Frank Bridoux |
| Author | Alain Mangé |
| Author | Ahmet Dogan |
| Author | Jean-Michel Goujon |
| Author | Marie Lhomme |
| Author | Carolane Dauteuille |
| Author | Michèle Chabert |
| Author | Riccardo Porcari |
| Author | Christopher A. Waudby |
| Author | Annalisa Relini |
| Author | Philippa J. Talmud |
| Author | Oleg Kovrov |
| Author | Gunilla Olivecrona |
| Author | Monica Stoppini |
| Author | John Christodoulou |
| Author | Philip N. Hawkins |
| Author | Gilles Grateau |
| Author | Marc Delpech |
| Author | Anatol Kontush |
| Author | Julian D. Gillmore |
| Author | Athina D. Kalopissis |
| Author | Vittorio Bellotti |
| 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. |
| Publication | Nature Communications |
| Volume | 7 |
| Pages | 10353 |
| Date | Jan 21, 2016 |
| Journal Abbr | Nat Commun |
| Language | eng |
| DOI | 10.1038/ncomms10353 |
| ISSN | 2041-1723 |
| Library Catalog | PubMed |
| Extra | PMID: 26790392 PMCID: PMC4735822 |
| Tags | Adult, Aged, Aged, 80 and over, Amyloidosis, Apolipoprotein C-III, author, Base Sequence, Cardiovascular Diseases, Female, France, Humans, Hyperlipoproteinemias, Lipoproteins, HDL, Lipoproteins, VLDL, Male, Middle Aged, Molecular Sequence Data, Mutation, Missense, original, Pedigree, pp2i, top |
| Date Added | 2019/06/04 - 17:30:42 |
| Date Modified | 2020/01/14 - 18:45:25 |
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