Comparative Effects of Diet-Induced Lipid Lowering Versus Lipid Lowering Along With Apo A-I Milano Gene Therapy on Regression of Atherosclerosis

@article{Wang2016ComparativeEO,
  title={Comparative Effects of Diet-Induced Lipid Lowering Versus Lipid Lowering Along With Apo A-I Milano Gene Therapy on Regression of Atherosclerosis},
  author={Lai Wang and Fang Tian and Ana Arias and Mingjie Yang and Behrooz G Sharifi and Prediman K Shah},
  journal={Journal of Cardiovascular Pharmacology and Therapeutics},
  year={2016},
  volume={21},
  pages={320 - 328}
}
  • Lai Wang, Fang Tian, P. Shah
  • Published 1 May 2016
  • Biology, Medicine
  • Journal of Cardiovascular Pharmacology and Therapeutics
Apolipoprotein A-1 (Apo A-I) Milano, a naturally occurring Arg173 to Cys mutant of Apo A-1, has been shown to reduce atherosclerosis in animal models and in a small phase 2 human trial. We have shown the superior atheroprotective effects of Apo A-I Milano (Apo A-IM) gene compared to wild-type Apo A-I gene using transplantation of retrovirally transduced bone marrow in Apo A-I/Apo E null mice. In this study, we compared the effect of dietary lipid lowering versus lipid lowering plus Apo A-IM… 

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References

SHOWING 1-10 OF 19 REFERENCES
Effects of recombinant apolipoprotein A-I(Milano) on aortic atherosclerosis in apolipoprotein E-deficient mice.
TLDR
Recombinant A-I(Milano)/PC prevented progression of aortic atherosclerosis and reduced lipid and macrophage content of plaques in apo E-deficient mice despite severe hypercholesterolemia.
Gene transfer of wild-type apoA-I and apoA-I Milano reduce atherosclerosis to a similar extent
TLDR
Liver-directed AAV2.8-mediated gene transfer of wtApoA-I and ApoA-IM each significantly reduced atherosclerosis progression to a similar extent, a model which is most adequately mimicking the clinical setting.
Rapid reversal of endothelial dysfunction in hypercholesterolemic apolipoprotein E-null mice by recombinant apolipoprotein A-I(Milano)-phospholipid complex.
Wild-type apo A-I and apo A-IMilano gene transfer reduce native and transplant arteriosclerosis to a similar extent
TLDR
The current head-to-head comparison indicates that human apo A-IMilano transfer is not superior compared to wild-type human api A-I transfer.
Comparative Antiatherogenic Effects of Intravenous AAV8- and AAV2-Mediated ApoA-IMilano Gene Transfer in Hypercholesterolemic Mice
TLDR
Investigation of the antiatherogenic efficacy of ApoA-IM gene transfer using Recombinant adeno-associated virus (rAAV) 2 or rAAV8 as vectors in mice shows support for the potential feasibility of this approach for atheroprotection in humans.
AAV serotype-dependent apolipoprotein A-I Milano gene expression.
Recombinant apolipoprotein A-I Milano reduces intimal thickening after balloon injury in hypercholesterolemic rabbits.
TLDR
Findings are consistent with a direct vascular effect of apo A-I, which could have potential therapeutic implications in cholesterol-fed rabbits without a change in arterial total cholesterol content.
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