Hyperlipidemia and atherosclerotic lesion development in LDL receptor-deficient mice fed defined semipurified diets with and without cholate

被引:138
作者
Lichtman, AH
Clinton, SK
Iiyama, K
Connelly, PW
Libby, P
Cybulsky, MI
机构
[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA
[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Vasc Res, Boston, MA 02215 USA
[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Vasc Med & Atherosclerosis Unit, Boston, MA 02215 USA
[4] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc,Dept Med, Boston, MA 02215 USA
[5] Ohio State Univ, Arthur G James Canc Hosp & Res Inst, Columbus, OH 43210 USA
[6] Univ Toronto, Toronto Hosp, Res Ctr, Dept Lab Med & Pathobiol, Toronto, ON, Canada
[7] Univ Toronto, St Michaels Hosp, Dept Lab Med & Pathobiol, Toronto, ON, Canada
[8] Univ Toronto, St Michaels Hosp, Dept Med, Toronto, ON, Canada
[9] Univ Toronto, St Michaels Hosp, Dept Biochem, Toronto, ON, Canada
关键词
atherosclerosis; LDL receptor; dietary lipids; cholesterol; mice;
D O I
10.1161/01.ATV.19.8.1938
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Past studies of atherosclerosis in mice have used chow-based diets supplemented with cholesterol, lipid, and sodium cholate to overcome species resistance to lesion formation. Similar diets have been routinely used in studies with LDL receptor-deficient (LDLR-/-) mice. The nonphysiological nature and potential toxicity of cholate-containing diets; have led to speculation that atherogenesis in these mice may not accurately reflect the human disease process. We have designed a semipurified AIN-76A-based diet that can be fed in powdered, pelleted, or liquid form and manipulated for the precise evaluation of diet-genetic interactions in murine atherosclerosis. LDLR-/- mice were randomly assigned among 4 diets (n=6/diet) as follows: 1, control, 10% kcal lipid; 2, high fat (40% kcal), moderate cholesterol (0.5% by weight); 3, high fat, high cholesterol (1.25% by weight); and 4, high fat, high cholesterol, and 0.5% (wt/wt) sodium cholate. Fasting serum cholesterol was increased in all choleslerol-supplemented mice compared with controls after 6 or 12 weeks of feeding (P<0.01). The total area of oil red O-stained atherosclerotic lesions was determined from digitally scanned photographs. In contrast to the control group, ail mice in cholesterol-supplemented dietary groups 2 to 4 had lesions involving 7.01% to 12.79% area of the thoracic and abdominal aorta at 12 weeks (P<0.002, for each group versus control). The distribution pattern of atherosclerotic lesions was highly reproducible and comparable. The histological features of lesions in mice fed cholate-Eree or cholate-containing diets were similar, This study shows that sodium cholate is not necessary for the formation of atherosclerosis in LDLR-/- mice and that precisely defined semipurified diets are a valuable tool for the examination of diet-gene interactions.
引用
收藏
页码:1938 / 1944
页数:7
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