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 & 7 others Philip N. Hawkins, Gilles Grateau, Marc Delpech, Anatol Kontush, Julian D. Gillmore, Athina D. Kalopissis, Vittorio Bellotti

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Article number10353
JournalNature Communications
Volume7
StatePublished - Jan 21 2016

Fingerprint

Familial Amyloidosis
Apolipoprotein C-III
lipoproteins
Lipoproteins
Amyloid
causes
mutations
profiles
lipids
Amyloidosis
therapy
Renal Insufficiency
proteins
Amyloidogenic Proteins
Fibric Acids
VLDL Lipoproteins
HDL Lipoproteins
Triglycerides
Transcription
Lipids

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Valleix, S., Verona, G., Jourde-Chiche, N., Nédelec, B., Mangione, P. P., Bridoux, F., ... Bellotti, V. (2016). D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile. Nature Communications, 7, [10353].

D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile. / Valleix, Sophie; Verona, Guglielmo; Jourde-Chiche, Noémie; Nédelec, Brigitte; Mangione, P. Patrizia; Bridoux, Frank; Mangé, Alain; Dogan, Ahmet; Goujon, Jean Michel; Lhomme, Marie; Dauteuille, Carolane; Chabert, Michèle; Porcari, Riccardo; Waudby, Christopher A.; Relini, Annalisa; Talmud, Philippa J.; Kovrov, Oleg; Olivecrona, Gunilla; Stoppini, Monica; Christodoulou, John; Hawkins, Philip N.; Grateau, Gilles; Delpech, Marc; Kontush, Anatol; Gillmore, Julian D.; Kalopissis, Athina D.; Bellotti, Vittorio.

In: Nature Communications, Vol. 7, 10353, 21.01.2016.

Research output: Contribution to journalArticle

Valleix, S, Verona, G, Jourde-Chiche, N, Nédelec, B, Mangione, PP, Bridoux, F, Mangé, A, Dogan, A, Goujon, JM, Lhomme, M, Dauteuille, C, Chabert, M, Porcari, R, Waudby, CA, Relini, A, Talmud, PJ, Kovrov, O, Olivecrona, G, Stoppini, M, Christodoulou, J, Hawkins, PN, Grateau, G, Delpech, M, Kontush, A, Gillmore, JD, Kalopissis, AD & Bellotti, V 2016, 'D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile', Nature Communications, vol. 7, 10353.
Valleix, Sophie ; Verona, Guglielmo ; Jourde-Chiche, Noémie ; Nédelec, Brigitte ; Mangione, P. Patrizia ; Bridoux, Frank ; Mangé, Alain ; Dogan, Ahmet ; Goujon, Jean Michel ; Lhomme, Marie ; Dauteuille, Carolane ; Chabert, Michèle ; Porcari, Riccardo ; Waudby, Christopher A. ; Relini, Annalisa ; Talmud, Philippa J. ; Kovrov, Oleg ; Olivecrona, Gunilla ; Stoppini, Monica ; Christodoulou, John ; Hawkins, Philip N. ; Grateau, Gilles ; Delpech, Marc ; Kontush, Anatol ; Gillmore, Julian D. ; Kalopissis, Athina D. ; Bellotti, Vittorio. / D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile. In: Nature Communications. 2016 ; Vol. 7.
@article{5fd6e657dc53495fa25ed161977fc814,
title = "D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile",
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.",
author = "Sophie Valleix and Guglielmo Verona and No{\'e}mie Jourde-Chiche and Brigitte N{\'e}delec and Mangione, {P. Patrizia} and Frank Bridoux and Alain Mang{\'e} and Ahmet Dogan and Goujon, {Jean Michel} and Marie Lhomme and Carolane Dauteuille and Mich{\`e}le Chabert and Riccardo Porcari and Waudby, {Christopher A.} and Annalisa Relini and Talmud, {Philippa J.} and Oleg Kovrov and Gunilla Olivecrona and Monica Stoppini and John Christodoulou and Hawkins, {Philip N.} and Gilles Grateau and Marc Delpech and Anatol Kontush and Gillmore, {Julian D.} and Kalopissis, {Athina D.} and Vittorio Bellotti",
year = "2016",
month = "1",
day = "21",
language = "English (US)",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

AU - Valleix, Sophie

AU - Verona, Guglielmo

AU - Jourde-Chiche, Noémie

AU - Nédelec, Brigitte

AU - Mangione, P. Patrizia

AU - Bridoux, Frank

AU - Mangé, Alain

AU - Dogan, Ahmet

AU - Goujon, Jean Michel

AU - Lhomme, Marie

AU - Dauteuille, Carolane

AU - Chabert, Michèle

AU - Porcari, Riccardo

AU - Waudby, Christopher A.

AU - Relini, Annalisa

AU - Talmud, Philippa J.

AU - Kovrov, Oleg

AU - Olivecrona, Gunilla

AU - Stoppini, Monica

AU - Christodoulou, John

AU - Hawkins, Philip N.

AU - Grateau, Gilles

AU - Delpech, Marc

AU - Kontush, Anatol

AU - Gillmore, Julian D.

AU - Kalopissis, Athina D.

AU - Bellotti, Vittorio

PY - 2016/1/21

Y1 - 2016/1/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84955513374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84955513374&partnerID=8YFLogxK

M3 - Article

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 10353

ER -