PMID- 15496963
OWN - NLM
STAT- MEDLINE
DCOM- 20050216
LR  - 20131121
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 11
IP  - 24
DP  - 2004 Dec
TI  - Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits 
      atherosclerosis in apolipoprotein E-deficient mice.
PG  - 1772-9
AB  - 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.
FAU - Yoshioka, T
AU  - Yoshioka T
AD  - Division of Cardiovascular Medicine, Jichi Medical School, Tochigi, Japan.
FAU - Okada, T
AU  - Okada T
FAU - Maeda, Y
AU  - Maeda Y
FAU - Ikeda, U
AU  - Ikeda U
FAU - Shimpo, M
AU  - Shimpo M
FAU - Nomoto, T
AU  - Nomoto T
FAU - Takeuchi, K
AU  - Takeuchi K
FAU - Nonaka-Sarukawa, M
AU  - Nonaka-Sarukawa M
FAU - Ito, T
AU  - Ito T
FAU - Takahashi, M
AU  - Takahashi M
FAU - Matsushita, T
AU  - Matsushita T
FAU - Mizukami, H
AU  - Mizukami H
FAU - Hanazono, Y
AU  - Hanazono Y
FAU - Kume, A
AU  - Kume A
FAU - Ookawara, S
AU  - Ookawara S
FAU - Kawano, M
AU  - Kawano M
FAU - Ishibashi, S
AU  - Ishibashi S
FAU - Shimada, K
AU  - Shimada K
FAU - Ozawa, K
AU  - Ozawa K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Apolipoproteins E)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipids)
RN  - 130068-27-8 (Interleukin-10)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Aorta/metabolism
MH  - Apolipoproteins E/*deficiency
MH  - Arteriosclerosis/immunology/metabolism/pathology/*prevention & control
MH  - Cell Line
MH  - Chemokine CCL2/metabolism
MH  - Cholesterol/metabolism
MH  - Gene Transfer Techniques
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/*genetics
MH  - Hydroxymethylglutaryl CoA Reductases/metabolism
MH  - Interleukin-10/biosynthesis/*genetics
MH  - Lipids/blood
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
EDAT- 2004/10/22 09:00
MHDA- 2005/02/17 09:00
CRDT- 2004/10/22 09:00
PHST- 2004/10/22 09:00 [pubmed]
PHST- 2005/02/17 09:00 [medline]
PHST- 2004/10/22 09:00 [entrez]
AID - 3302348 [pii]
AID - 10.1038/sj.gt.3302348 [doi]
PST - ppublish
SO  - Gene Ther. 2004 Dec;11(24):1772-9. doi: 10.1038/sj.gt.3302348.