Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice

Gene Ther. 2004 Dec;11(24):1772-9. doi: 10.1038/


Inflammation is a major contributor to atherosclerosis by its effects on arterial wall biology and lipoprotein metabolism. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that may modulate the atherosclerotic disease process. We investigated the effects of adeno-associated virus (AAV) vector-mediated gene transfer of IL-10 on atherogenesis in apolipoprotein E (ApoE)-deficient mice. A murine myoblast cell line, C2C12, transduced with AAV encoding murine IL-10 (AAV2-mIL10) secreted substantial amounts of IL-10 into conditioned medium. The production of monocyte chemoattractant protein-1 (MCP-1) by the murine macrophage cell line, J774, was significantly inhibited by conditioned medium from AAV2-mIL10-transduced C2C12 cells. ApoE-deficient mice were injected with AAV5-mIL10 into their anterior tibial muscle at 8 weeks of age. The expression of MCP-1 in the vascular wall of the ascending aorta and serum MCP-1 concentration were decreased in AAV5-mIL10-transduced mice compared with AAV5-LacZ-transduced mice. Oil red-O staining of the ascending aorta revealed that IL-10 gene transfer resulted in a 31% reduction in plaque surface area. Serum cholesterol concentrations were also significantly reduced in AAV5-mIL10-transduced mice. To understand the cholesterol-lowering mechanism of IL-10, we measured the cellular cholesterol level in HepG2 cells, resulting in its significant decrease by the addition of IL-10 in a dose-dependent manner. Furthermore, IL-10 suppressed HMG-CoA reductase expression in the HepG2 cells. These observations suggest that intramuscular injection of AAV5-mIL10 into ApoE-deficient mice inhibits atherogenesis through anti-inflammatory and cholesterol-lowering effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Aorta / metabolism
  • Apolipoproteins E / deficiency*
  • Arteriosclerosis / immunology
  • Arteriosclerosis / metabolism
  • Arteriosclerosis / pathology
  • Arteriosclerosis / prevention & control*
  • Cell Line
  • Chemokine CCL2 / metabolism
  • Cholesterol / metabolism
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics*
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics*
  • Lipids / blood
  • Male
  • Mice
  • Mice, Inbred C57BL


  • Apolipoproteins E
  • Chemokine CCL2
  • Lipids
  • Interleukin-10
  • Cholesterol
  • Hydroxymethylglutaryl CoA Reductases