| Added by | mollevi |
|---|---|
| Last modified by | pcoopman |
| Group name | EquipePC |
| 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 | S. Valleix |
| Author | G. Verona |
| Author | N. Jourde-Chiche |
| Author | B. Nedelec |
| Author | P. P. Mangione |
| Author | F. Bridoux |
| Author | A. Mange |
| Author | A. Dogan |
| Author | J. M. Goujon |
| Author | M. Lhomme |
| Author | C. Dauteuille |
| Author | M. Chabert |
| Author | R. Porcari |
| Author | C. A. Waudby |
| Author | A. Relini |
| Author | P. J. Talmud |
| Author | O. Kovrov |
| Author | G. Olivecrona |
| Author | M. Stoppini |
| Author | J. Christodoulou |
| Author | P. N. Hawkins |
| Author | G. Grateau |
| Author | M. Delpech |
| Author | A. Kontush |
| Author | J. D. Gillmore |
| Author | A. D. Kalopissis |
| Author | V. 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 | Nat Commun |
| Volume | 7 |
| Pages | 10353 |
| Date | 2016 |
| Journal Abbr | Nature communications |
| DOI | 10.1038/ncomms10353 |
| ISSN | 2041-1723 (Electronic) 2041-1723 (Linking) |
| Tags | clinic |
| Date Added | 2018/11/14 - 12:07:50 |
| Date Modified | 2019/05/16 - 15:50:32 |
| Notes and Attachments | (Note) (Note) 26790392 (Attachment) |
Institut de Recherche en Cancérologie de
