Inhibition of atherogenesis in LDLR knockout mice by systemic delivery of adeno-associated virus type 2-hIL-10

Atherosclerosis. 2006 Sep;188(1):19-27. doi: 10.1016/j.atherosclerosis.2005.10.029. Epub 2005 Nov 21.


Atherosclerosis is an inflammatory disease of the arteries. Interleukin-10 (IL-10) is known to be an anti-inflammatory cytokine which might be useful for counteracting the development of atherosclerosis. As long-term systemic cytokine delivery is prohibitively expensive, gene therapy might be a suitable approach. To test this idea, low-density lipoprotein receptor (LDLR) knockout mice were injected with recombinant adeno-associated virus type 2 (AAV)/interleukin-10 virus or AAV/granulocyte macrophage-colony stimulating factor (GM-CSF) virus and then put on a high-cholesterol diet. Upon harvesting the animals at 18 weeks, elevated blood lipids could be documented and AAV/IL-10 and AAV/GM-CSF DNA and mRNA could be found in various mouse organs. The mice receiving the AAV/IL-10 virus had significantly lower levels of atherogenesis (Sudan IV-staining and histology) than the untreated or the AAV/GM-CSF-treated animals, dropping from 53% to 17% (p < 0.05). The aortas of the AAV/IL-10-treated animals displayed higher IL-10 expression and lower CD68 and nitrotyrosine expression. These data are similar to those of Yoshioka et al. [Yoshioka, T, Okada, T, Maeda, Y, et al. Adeno-associatedvirus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice. Gene Ther 2004;11:1772-9] in which AAV/IL-10 was delivered into the tibial muscle of ApoE-deficient mice, instead of tail vein injection used here. These data indicate that systemic AAV/IL-10 gene delivery, with resulting inhibition of inflammation and oxidative stress, was able to limit atherogenesis, and suggest that this approach is worthy of further study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / chemistry
  • Atherosclerosis / therapy*
  • Cholesterol, Dietary / administration & dosage
  • DNA / analysis
  • Dependovirus / genetics
  • Genetic Therapy*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Humans
  • Interleukin-10 / analysis
  • Interleukin-10 / genetics*
  • Mice
  • Mice, Knockout
  • RNA, Messenger / analysis
  • Receptors, LDL / genetics


  • Cholesterol, Dietary
  • RNA, Messenger
  • Receptors, LDL
  • Interleukin-10
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • DNA