title: Defining the atherogenicity of large and small lipoproteins containing apolipoprotein B100.
abstract: Apo-E-deficient apo-B100-only mice (APOE:(-/-)APOB:(100/100)) and LDL receptor-deficient apo-B100-only mice (LDLR:(-/-)APOB:(100/100)) have similar total plasma cholesterol levels, but nearly all of the plasma cholesterol in the former animals is packaged in VLDL particles, whereas, in the latter, plasma cholesterol is found in smaller LDL particles. We compared the apo-B100-containing lipoprotein populations in these mice to determine their relation to susceptibility to atherosclerosis. The median size of the apo-B100-containing lipoprotein particles in APOE:(-/-)APOB:(100/100) plasma was 53.4 nm versus only 22.1 nm in LDLR:(-/-)APOB:(100/100) plasma. The plasma levels of apo-B100 were three- to fourfold higher in LDLR:(-/-)APOB:(100/100) mice than in APOE:(-/-)APOB:(100/100) mice. After 40 weeks on a chow diet, the LDLR:(-/-)APOB:(100/100) mice had more extensive atherosclerotic lesions than APOE:(-/-)APOB:(100/100) mice. The aortic DNA synthesis rate and the aortic free and esterified cholesterol contents were also higher in the LDLR:(-/-)APOB:(100/100) mice. These findings challenge the notion that all non-HDL lipoproteins are equally atherogenic and suggest that at a given cholesterol level, large numbers of small apo-B100-containing lipoproteins are more atherogenic than lower numbers of large apo-B100-containing lipoproteins.
authors: Gladstone Institute of Cardiovascular Disease, Cardiovascular Research Institute, University of California, San Francisco, California, USA. mveniant@amgen.com
authors: M M
authors: MM
authors: Véniant
authors: M A
authors: MA
authors: Sullivan
authors: S K
authors: SK
authors: Kim
authors: P
authors: P
authors: Ambroziak
authors: A
authors: A
authors: Chu
authors: M D
authors: MD
authors: Wilson
authors: M K
authors: MK
authors: Hellerstein
authors: L L
authors: LL
authors: Rudel
authors: R L
authors: RL
authors: Walzem
authors: S G
authors: SG
authors: Young
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000097:blood / Q000378:metabolism*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006651:Histocytochemistry; D008074:Lipoproteins / Q000097:blood / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010316:Particle Size; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D012307:Risk Factors
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008074:Lipoproteins; D011973:Receptors, LDL; D004247:DNA; D002784:Cholesterol