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Apolipoprotein A-I Deficiency Results in Markedly Increased Atherosclerosis in Mice Lacking the LDL Receptor

2003; Lippincott Williams & Wilkins; Volume: 23; Issue: 10 Linguagem: Inglês

10.1161/01.atv.0000092328.66882.f5

1524-4636

Ryan E. Moore, Masa‐aki Kawashiri, Ken Kitajima, Anthony Secreto, John S. Millar, Domenico Praticò, Daniel McConnell,

Peroxisome Proliferator-Activated Receptors

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.