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: M M Véniant, M A Sullivan, S K Kim, P Ambroziak, A Chu, M D Wilson, M K Hellerstein, L L Rudel, R L Walzem, S G Young
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 106 Issue 12 Pg. 1501-10 (Dec 2000) ISSN: 0021-9738 [Print] United States
• PMID: 11120757 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Apolipoprotein B-100
• Apolipoproteins B
• Apolipoproteins E
• Cholesterol Esters
• Lipoproteins
• Receptors, LDL
• DNA
• Cholesterol

Topics

• Animals
• Aorta (metabolism, pathology)
• Apolipoprotein B-100
• Apolipoproteins B (blood, metabolism)
• Apolipoproteins E (deficiency, genetics, physiology)
• Arteriosclerosis (etiology, genetics, metabolism, pathology)
• Cholesterol (blood, metabolism)
• Cholesterol Esters (metabolism)
• DNA (biosynthesis)
• Female
• Histocytochemistry
• Lipoproteins (blood, chemistry, metabolism)
• Mice
• Mice, Knockout
• Particle Size
• Receptors, LDL (deficiency, genetics, physiology)
• Risk Factors