Decreased susceptibility to diet-induced atherosclerosis in human apolipoprotein A-II transgenic mice

Studies performed in vivo have been controversial regarding the implication of human apolipoprotein (apo)A-II in the atherogoenic process. Expression of human apoA-II in transgenic mice fed a chow diet leads to (1) a bimodal distribution of high density lipoprotein (HDL) size as in humans, (2) a red uction in total cholesterol concentration that is mainly due to a reduction in non-HDL cholesterol level, and (3) a dramatic reduction in mouse endoge nous apoA-I and apoA-II. After 20 weeks on an atherogenic diet, transgenic mice had reduced total cholesterol concentrations because of a reduction in cholesterol associated with all lipoprotein classes. Endogenous apoA-I and apoA-II were also dramatically decreased in transgenic mice. The mean area of atherosclerotic lesions was drastically decreased in transgenic mice (- 44%, P=0.0027) compared with control mice. The amount of aortic surface cov ered by lesions was positively correlated with very low density lipoprotein cholesterol (P<0.01) and intermediate density lipoprotein cholesterol leve ls (P<0.05). Transgenic mice were protected against the development of athe rosclerosis despite a marked decrease in HDL cholesterol and apoA-I concent rations. This protection may be related to the marked reduction in circulat ing low density lipoprotein (very low density and intermediate density lipo protein) levels in transgenic mice.