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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1914.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Ryan E. Moore; Masa-aki Kawashiri; Ken Kitajima; Anthony Secreto; John S. Millar; Domenico Pratico; Daniel J. Rader

From the University of Pennsylvania School of Medicine, Philadelphia, Pa.

Correspondence to Daniel J. Rader, University of Pennsylvania School of Medicine, 654 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104. E-mail rader{at}mail.med.upenn.edu

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.

Key Words: arteriosclerosis • apolipoproteins • cholesterol • lipids • oxidant stress

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