Journal
JOURNAL OF MOLECULAR MEDICINE-JMM
Volume 87, Issue 3, Pages 287-297Publisher
SPRINGER
DOI: 10.1007/s00109-008-0427-y
Keywords
Apo A-I-Milano; Gene transfer; Allograft vasculopathy; Endothelial progenitor cell; Atherosclerosis
Funding
- Fonds voor Wetenschappelijk Onderzoek- Vlaanderen [0564.05]
- Excellentiefinanciering KU Leuven [EF/05/013]
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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.
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