Wild-type apo A-I and apo A-IMilano gene transfer reduce native and transplant arteriosclerosis to a similar extent

Apolipoprotein (apo) A-I-Milano is an apo A-I mutant characterized by a cysteine for arginine substitution at position 173. Apo A-I-Milano carriers have much less atherosclerosis than expected from their low plasma high-density lipoprotein cholesterol levels, suggesting that this mutant may have superior atheroprotective properties. Here, we compare the effect of hepatocyte-directed gene transfer of wild-type human apo A-I and human apo A-I-Milano on endothelial progenitor cell (EPC) biology and on the progression of native atherosclerosis and allograft vasculopathy in C57BL/6 apo E-/- mice. Human apo A-I and apo A-I-Milano transfer resulted in an equivalent increase of EPC number and function as well as EPC incorporation and endothelial regeneration in allografts and inhibited the progression of native atherosclerosis and allograft vasculopathy to a similar extent. In conclusion, the current head-to-head comparison indicates that human apo A-I-Milano transfer is not superior compared to wild-type human apo A-I transfer.