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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
|
| pubmed:dateCreated |
1998-1-22
|
| pubmed:abstractText |
We showed earlier that the apolipoprotein A-I Leu159-->Arg mutation (apoA-IFin) results in dominantly inherited hypoalphalipoproteinemia. In the present study we investigated the effect of the apoA-IFin mutation on lipoprotein profile, apoA-I kinetics, lecithin:cholesterol acyltransferase (LCAT) activation, and cholesterol efflux in vitro. Carriers (n = 9) of the apoA-IFin mutation exhibited several lipoprotein abnormalities. The serum HDL cholesterol level was diminished to 20% of normal, and nondenaturing gradient gel electrophoresis of HDL showed disappearance of particles at the 9.0- to 12-nm size range (HDL2-type) and the presence of small 7.8- to 8.9-nm (mostly HDL3-type) particles only. HDL3-type particles from both the mutation carriers and nonaffected family members were similarly converted to large, HDL2-type particles by phospholipid transfer protein in vitro. Studies on apoA-I kinetics in four affected subjects favored accelerated catabolism of apoA-I. Experiments with reconstituted proteoliposomes showed that the capacity of apoA-IFin protein to activate LCAT was reduced to 40% of that of the wild-type apoA-I. The impact of the apoA-IFin protein on cholesterol efflux was examined in vitro using [3H]cholesterol-loaded human fibroblasts and three different cholesterol acceptors: (1) total HDL, (2) total apoA-I combined with phospholipid, and (3) apoA-I isoform (apoA-IFin or wild-type apoA-I isoform 1) combined with phospholipid. ApoA-IFin did not impair phospholipid binding or cholesterol efflux from fibroblasts to any of the acceptors used. Only one of the nine apoA-IFin carriers appears to have evidence of clinically manifested atherosclerosis. In conclusion, although the apoA-IFin mutation does not alter the properties of apoA-I involved in promotion of cholesterol efflux, its ability to activate LCAT in vitro is defective. In vivo, apoA-IFin was found to be associated with several lipoprotein composition rearrangements and increased catabolism of apoA-I.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoprotein A-I,
http://linkedlifedata.com/resource/pubmed/chemical/CETP protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol Ester Transfer Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, HDL,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylcholine-Sterol...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylcholines,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipid Transfer Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/Proteolipids,
http://linkedlifedata.com/resource/pubmed/chemical/proteoliposomes
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
1079-5642
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
17
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3021-32
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:9409289-Adolescent,
pubmed-meshheading:9409289-Adult,
pubmed-meshheading:9409289-Aged,
pubmed-meshheading:9409289-Apolipoprotein A-I,
pubmed-meshheading:9409289-Carrier Proteins,
pubmed-meshheading:9409289-Cholesterol,
pubmed-meshheading:9409289-Cholesterol Ester Transfer Proteins,
pubmed-meshheading:9409289-Enzyme Activation,
pubmed-meshheading:9409289-Female,
pubmed-meshheading:9409289-Fibroblasts,
pubmed-meshheading:9409289-Genotype,
pubmed-meshheading:9409289-Glycoproteins,
pubmed-meshheading:9409289-Humans,
pubmed-meshheading:9409289-Lipoproteins, HDL,
pubmed-meshheading:9409289-Male,
pubmed-meshheading:9409289-Membrane Proteins,
pubmed-meshheading:9409289-Middle Aged,
pubmed-meshheading:9409289-Particle Size,
pubmed-meshheading:9409289-Pedigree,
pubmed-meshheading:9409289-Phosphatidylcholine-Sterol O-Acyltransferase,
pubmed-meshheading:9409289-Phosphatidylcholines,
pubmed-meshheading:9409289-Phospholipid Transfer Proteins,
pubmed-meshheading:9409289-Phospholipids,
pubmed-meshheading:9409289-Point Mutation,
pubmed-meshheading:9409289-Proteolipids
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Apolipoprotein A-IFIN (Leu159-->Arg) mutation affects lecithin cholesterol acyltransferase activation and subclass distribution of HDL but not cholesterol efflux from fibroblasts.
|
| pubmed:affiliation |
Department of Medicine, University of Helsinki, Finland. Helena.Miettinen@helsinki.fi
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|