Antioxidative and antiatherosclerotic effects of human apolipoprotein A-IVin apolipoprotein E-deficient mice

Mice expressing human apolipoprotein A-IV (apoA-IV) mainly in the intestine were obtained in an apolipoprotein E-deficient (apoE(o)) background (apoA- IV/E-o mice). Quantification of aortic lesions and plasma lipid determinati on showed that compared with their control apoE(o) counterparts, the apoA-I VIE, mice are protected against atherosclerosis without an increase in HDL cholesterol, Because oxidized lipoproteins play an important role in athero genesis, we tested whether the protection observed in these animals is acco mpanied by an in vivo reduction of the oxidation parameters. The lag time i n the formation of conjugated dienes during copper-mediated oxidation, the aggregation state of LDL, and the presence of anti-oxidized LDL antibodies were measured. The presence of oxidized proteins in tissues and the presenc e of oxidation-specific epitopes in heart sections of atherosclerotic lesio ns were also analyzed. Except for lag time, the results showed that the oxi dation parameters were reduced in the apoA-IV/E-o mice compared with the ap oE(o) mice. This suggests that human apoA-IV acts in vivo as an antioxidant , In addition, human apoA-IV accumulation was detected in the atherosclerot ic lesions of apoA-IV/E-o mice, suggesting that apoA-IV may inhibit oxidati ve damage to local tissues, thus decreasing the progression of atherosclero sis.