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


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.
Moore
Ryan E
RE
University of Pennsylvania School of Medicine, 654 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104, USA.
Kawashiri
Masa-aki
MA
Kitajima
Ken
K
Secreto
Anthony
A
Millar
John S
JS
Pratico
Domenico
D
Rader
Daniel J
DJ
D000818:Animals; D016632:Apolipoprotein A-I / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D011973:Receptors, LDL; D014280:Triglycerides