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Decorin overexpression reduces atherosclerosis development in apolipoprotein E-deficient mice

      Abstract

      Atherosclerosis results from accumulation of macrophages and extracellular matrix in the arterial wall. Decorin, a small matrix proteoglycan, is able to regulate cell proliferation, migration and growth factors’ activity. We investigated the effect of decorin overexpression on atherosclerosis progression in apolipoprotein E-deficient (ApoE−/−) mice. Female ApoE−/− mice, 10 weeks old (early treatment, n = 20) and 20 weeks old (delayed treatment, n = 20) were administered intravenously with either an adenovirus (2.5 × 109 plaque-forming units/mouse) containing human decorin gene (Ad-Dcn) or β-galactosidase (LacZ), or PBS. Transgenic decorin was mainly expressed in the liver, and was secreted in the plasma up to 4 weeks. Six weeks after treatment, no significant difference in aortic root lesion size was observed between LacZ- and PBS-control groups. In contrast, Ad-Dcn-treated mice showed significantly reduced atherosclerotic lesions as compared to controls in both early and delayed treatment groups (2.9 ± 1.1% versus 5.5 ± 0.4%; p = 0.004 and 13.4 ± 1.3% versus 19.9 ± 1.41%; p = 0.009, respectively). In parallel, macrophage, gelatinase activity and collagen plaque content were also reduced. Interestingly, plasma triglycerides were reduced and decorin formed complexes with transforming growth factor-β1 (TGF-β1) that resulted in reduced circulating free-TGF-β1.
      In conclusion, systemic overexpression of decorin reduces inflammation, triglycerides and fibrosis in atherosclerotic plaques of ApoE−/− mice resulting in slowing down of disease progression.

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