Journal of lipid research, 2014-12, Vol.55 (12), p.2509-2520
2014
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Defective functionality of HDL particles in familial apoA-I deficiency: relevance of alterations in HDL lipidome and proteome[S]
- Ist Teil von
- Journal of lipid research, 2014-12, Vol.55 (12), p.2509-2520
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2014
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- To evaluate functional and compositional properties of HDL in subjects from a kindred of genetic apoA-I deficiency, two homozygotes and six heterozygotes, with a nonsense mutation at APOA1 codon -2, Q[-2]X, were recruited together with age- and sex-matched healthy controls (n = 11). Homozygotes displayed undetectable plasma levels of apoA-I and reduced levels of HDL-cholesterol (HDL-C) and apoC-III (5.4% and 42.6% of controls, respectively). Heterozygotes displayed low HDL-C (21 ± 9 mg/dl), low apoA-I (79 ± 24 mg/dl), normal LDL-cholesterol (132 ± 25 mg/dl), and elevated TG (130 ± 45 mg/dl) levels. Cholesterol efflux capacity of ultracentrifugally isolated HDL subpopulations was reduced (up to −25%, P < 0.01, on a glycerophospholipid [GP] basis) in heterozygotes versus controls. Small, dense HDL3 and total HDL from heterozygotes exhibited diminished antioxidative activity (up to −48%, P < 0.001 on a total mass basis) versus controls. HDL subpopulations from both homozygotes and heterozygotes displayed altered chemical composition, with depletion in apoA-I, GP, and cholesteryl ester; enrichment in apoA-II, free cholesterol, and TG; and altered phosphosphingolipidome. The defective atheroprotective activities of HDL were correlated with altered lipid and apo composition. These data reveal that atheroprotective activities of HDL particles are impaired in homozygous and heterozygous apoA-I deficiency and are intimately related to marked alterations in protein and lipid composition.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-2275eISSN: 1539-7262DOI: 10.1194/jlr.M051631Titel-ID: cdi_doaj_primary_oai_doaj_org_article_18217a71a2294fb0940deceb284fb8da
- Format
- –
- Schlagworte
- Adult, antioxidative activity, apolipoprotein A-I, Apolipoprotein A-I - blood, Apolipoprotein A-I - deficiency, Apolipoprotein A-I - genetics, Apolipoprotein A-I - metabolism, Apolipoprotein C-III - blood, Apolipoprotein C-III - metabolism, Brazil, cellular cholesterol efflux, Cholesterol Ester Transfer Proteins - blood, Cholesterol Ester Transfer Proteins - metabolism, Cholesterol Esters - blood, Cholesterol Esters - metabolism, Cholesterol, HDL - blood, Cholesterol, HDL - metabolism, Cholesterol, LDL - blood, Cholesterol, LDL - metabolism, Codon, Nonsense, familial deficiency, Family Health, Female, genetics, HDL functionality, Heterozygote, high density lipoprotein, Homozygote, Humans, Hypoalphalipoproteinemias - blood, Hypoalphalipoproteinemias - genetics, Hypoalphalipoproteinemias - metabolism, lipidomics, Lipoproteins, HDL - blood, Lipoproteins, HDL - metabolism, Lipoproteins, HDL3 - blood, Lipoproteins, HDL3 - metabolism, Male, Phospholipids - blood, Phospholipids - metabolism, Sphingolipids - blood, Sphingolipids - metabolism, Triglycerides - blood, Triglycerides - metabolism