Apolipoprotein A-I deficiency results in markedly increased atherosclerosis in mice lacking the LDL receptor

被引:80
作者
Moore, RE [1 ]
Kawashiri, MA [1 ]
Kitajima, K [1 ]
Secreto, A [1 ]
Millar, JS [1 ]
Pratico, D [1 ]
Rader, DJ [1 ]
机构
[1] Univ Penn, Sch Med, Philadelphia, PA 19104 USA
关键词
arteriosclerosis; apolipoproteins; cholesterol; lipids; oxidant stress;
D O I
10.1161/01.ATV.0000092328.66882.F5
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective - An inverse and independent association between plasma levels of apolipoprotein (apo) A-I and coronary heart disease in humans is well established. ApoA-I is the primary protein component of HDL and is thought to play an important role in mediating several of the atheroprotective effects of HDL. However, studies of the effects of apoA-I deficiency on the development of atherosclerosis in mice have not been definitive. We examined the effects of apoA-I deficiency on plasma lipids and atherosclerosis in LDL receptor - deficient mice fed a chow diet for up to 22 months. Methods and Results - Both apoA-I -deficient (apoA- I-/-)/ LDL receptor-deficient (LDLR-/-) and LDLR-/- mice had a similar moderate elevation of non-HDL cholesterol (non-HDL-C). Unlike previous studies of apoA-I deficiency in which the HDL-C levels were extremely low, the apoA-I-/-/LDLR-/- mice in this study had substantial levels of HDL-C that were similar to wild-type mice. Despite similar levels of non-HDL-C and substantial levels of HDL-C, apoA- I-/-/ LDLR-/- mice develop significantly more atherosclerosis (up to a 5-fold increase) and oxidant stress (39% increase) than LDLR-/- mice. Conclusions - These results demonstrate that despite normal levels of HDL-C, apoA- I deficiency is associated with a significant loss of protection from the formation of atherosclerosis in LDLR-/- mice fed a chow diet.
引用
收藏
页码:1914 / 1920
页数:7
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