C3H apoE(-/-) mice have less atherosclerosis than C57BL apoE(-/-) mice despite having a more atherogenic serum lipid profile.
Wild-type C57BL mice are known to be susceptible to diet-induced atherosclerosis, whilst C3H mice are resistant. We investigated the effect of these background strains on the hyperlipidaemia and atherosclerosis that develops in mice deficient in apolipoprotein E (apoE(-/-)). Male and female apoE(-/-) mice on C3H/HeNHsd (C3H) and C57BL/6J (C57) backgrounds were fed atherogenic Western diet for 12 weeks. Serum cholesterol and triglyceride concentrations were measured and atherosclerosis quantified in the aortic sinus. C3H apoE(-/-) mice fed normal diet had 1.5 2 fold higher serum cholesterol levels than C57 apoE(-/-) mice and 4-5 fold higher serum triglyceride concentrations. Feeding Western diet caused a 4-5 fold increase in serum cholesterol in all mice, but levels of triglyceride were either attenuated or were unaffected in C3H apoE(-/-) and C57 apoE(-/-) mice, respectively. C3H apoE(-/-) mice had approximately 2 fold higher serum cholesterol and 4 fold higher triglyceride concentrations than the C57 apoE(-/-) mice throughout the study. Serum triglyceride concentrations were 35-108% higher in male C3H apoE(-/-) than female C3H apoE(-/-) mice. Most of the lipids were present in the very low density lipoprotein (VLDL)/chylomicron fraction in both strains of mice whether they were fed normal or Western diet. Notwithstanding the lower plasma lipid concentrations, atherosclerotic lesion areas were more than 2-fold larger in C57 apoE(-/-) than in C3H apoE(-/-) mice (males 68 +/- 11 x 10(3) vs 30 +/- 6 x 10(3) females 102 +/- 12 x 10(3) vs 41 +/- 8 x 10(3) microm2. mean +/- SEM).
Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. david_c_grimsditch@sbphrd.com
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Grimsditch
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Penfold
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Latcham
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Vidgeon-Hart
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Groot
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Benson
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D004435:Eating; D005260:Female; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H / Q000502:physiology*; D008810:Mice, Inbred C57BL / Q000502:physiology*; D009994:Osmolar Concentration; D012727:Sex Characteristics; D013045:Species Specificity; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008055:Lipids; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol