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D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile
- Source :
- Nature Communications, Nature Communications, 2016, pp.10353. ⟨10.1038/ncomms10353⟩, Scopus-Elsevier, Nature Communications, Nature Publishing Group, 2016, pp.10353, Nature Communications, Vol 7, Iss 1, Pp 1-14 (2016), Nature Communications, Nature Publishing Group, 2016, pp.10353. ⟨10.1038/ncomms10353⟩
- Publication Year :
- 2016
- Publisher :
- HAL CCSD, 2016.
-
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.<br />Decrease in Apolipoprotein C-III (ApoC-III) yields a cardioprotective lipoprotein profile. Here, Valleix et al. reveal a novel ApoC-III variant conferring low plasma ApoC-III concentration and cardioprotection despite renal insufficiency, and, unexpectedly, causing dominant hereditary systemic amyloidosis due to its fibrillogenic nature.
- Subjects :
- Adult
Male
Hyperlipoproteinemias
Science
[SDV]Life Sciences [q-bio]
Molecular Sequence Data
Mutation, Missense
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Lipoproteins, VLDL
bcs
Article
LIPASE ACTIVITY
OF-FUNCTION MUTATIONS
Humans
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Aged
Aged, 80 and over
Apolipoprotein C-III
CELLULAR CHOLESTEROL EFFLUX
[ SDV ] Life Sciences [q-bio]
Base Sequence
Amyloidosis
Middle Aged
LIPID-BINDING
ANTIOXIDATIVE ACTIVITY
Pedigree
[SDV] Life Sciences [q-bio]
HDL PARTICLES
A-I
ELEVATED OXIDATIVE STRESS
Cardiovascular Diseases
Female
lipids (amino acids, peptides, and proteins)
France
Lipoproteins, HDL
DENSE LDL
TRIGLYCERIDE-RICH LIPOPROTEINS
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, Nature Communications, 2016, pp.10353. ⟨10.1038/ncomms10353⟩, Scopus-Elsevier, Nature Communications, Nature Publishing Group, 2016, pp.10353, Nature Communications, Vol 7, Iss 1, Pp 1-14 (2016), Nature Communications, Nature Publishing Group, 2016, pp.10353. ⟨10.1038/ncomms10353⟩
- Accession number :
- edsair.pmid.dedup....194cade83039b6591442874b6285d900