Common variants of apolipoprotein A-IV differ in their ability to inhibit low density lipoprotein oxidation

Abstract 

Apolipoprotein A-IV (apoA-IV) inhibits lipid peroxidation, thus demonstrating potential anti-atherogenic properties. The aim of this study was to investigate how the inhibition of low density lipoprotein (LDL) oxidation was influenced by common apoA-IV isoforms. Recombinant wild type apoA-IV (100μg/ml) significantly inhibited the oxidation of LDL (50μgprotein/ml) by 5μM CuSO₄ (P<0.005), but not by 100μM CuSO₄, suggesting that it may act by binding copper ions. ApoA-IV also inhibited the oxidation of LDL by the water-soluble free-radical generator 2,2′-azobis(amidinopropane) dihydrochloride (AAPH; 1mM), as shown by the two-fold increase in the time for half maximal conjugated diene formation (T_1/2; P<0.05) suggesting it can also scavenge free radicals in the aqueous phase. Compared to wild type apoA-IV, apoA-IV-S347 decreased T_1/2 by 15% (P=0.036) and apoA-IV-H360 increased T_1/2 by 18% (P=0.046). All apoA-IV isoforms increased the relative electrophoretic mobility of native LDL, suggesting apoA-IV can bind to LDL and acts as a site-specific antioxidant. The reduced inhibition of LDL oxidation by apoA-IV-S347 compared to wild type apoA-IV may account for the previous association of the APOA4 S347 variant with increased CHD risk and oxidative stress.

Keywords: Atherosclerosis, apoA-IV, Conjugated dienes, Copper, Lipid hydroperoxides, Oxidised low density lipoprotein