title: Global functional knockdown of ATP binding cassette transporter A1 stimulates development of atherosclerosis in apoE K/O mice.
abstract: ABCA1 is a key element of cellular cholesterol homeostasis. ApoE K/O mice fed with high-fat diet were infused with anti-ABCA1 antibody or control IgM. Infusion of anti-ABCA1 antibody led to 72% increase in the area of atherosclerotic plaque in aorta. After 16 weeks on high-fat diet plasma level of high density lipoprotein cholesterol (HDL-C) was reduced in control group, but was unchanged in mice infused with anti-ABCA1 antibody. Total plasma cholesterol level was elevated while the capacity of plasma to support cholesterol efflux ex vivo was reduced after 16 weeks on high-fat diet; the effects were similar in the two groups. We conclude that functional blocking of ABCA1-dependent cholesterol efflux stimulates development of atherosclerosis in apoE K/O mice independently from HDL-C levels.
authors.affiliation: Baker Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Nigora
authors.initials: N
authors.lastname: Mukhamedova
authors.forename: Wilissa
authors.initials: W
authors.lastname: D'Souza
authors.forename: Hann
authors.initials: H
authors.lastname: Low
authors.forename: Rajitha
authors.initials: R
authors.lastname: Kesani
authors.forename: Giovanna
authors.initials: G
authors.lastname: Chimini
authors.forename: Dmitri
authors.initials: D
authors.lastname: Sviridov
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D051379:Mice; D018345:Mice, Knockout
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001057:Apolipoproteins E; D002784:Cholesterol