Decorin overexpression reduces atherosclerosis development in apolipoprotein E-deficient mice
Decorin overexpression reduces atherosclerosis development in apolipoprotein E-deficient mice
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DOI：
10.1016/j.atherosclerosis.2005.08.023
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发表时间：
2006-07-01
期刊：
影响因子：
5.3
通讯作者：
Lafont, Antoine
中科院分区：
文献类型：
--
作者：
Al Haj Zen, Ayman;Caligiuri, Giuseppina;Lafont, Antoine
动脉粥样硬化是由动脉壁中巨噬细胞和细胞外基质的积累引起的。核心蛋白聚糖是一种小基质蛋白聚糖，能够调节细胞增殖、迁移和生长因子的活性。我们研究了核心蛋白聚糖过表达对载脂蛋白 E 缺陷 (ApoE(-/-)) 小鼠动脉粥样硬化进展的影响。 10周龄（早期治疗，n = 20）和20周龄（延迟治疗，n = 20）雌性ApoE（-/-）小鼠静脉注射含有人核心蛋白聚糖基因Ad-Dcn的腺病毒（2.5 x 10（9）噬菌斑形成单位/小鼠）或β-半乳糖苷酶（LacZ）或PBS。转基因核心蛋白聚糖主要在肝脏中表达，并在血浆中分泌长达4周。治疗六周后，LacZ 对照组和 PBS 对照组之间主动脉根部病变大小没有观察到显着差异。相反，在早期和延迟治疗组中，与对照组相比，Ad-Dcn治疗小鼠的动脉粥样硬化病变显着减少（分别为2.9 +/- 1.1% vs 5.5 +/- 0.4%；p = 0.004；13.4 +/- 1.3% vs 19.9 +/- 1.41%；p = 0.009）。与此同时，巨噬细胞、明胶酶活性和胶原斑含量也降低。有趣的是，血浆甘油三酯降低，核心蛋白聚糖与转化生长因子-β(1) (TGF-β(1)) 形成复合物，导致循环游离 TGF-β(1) 减少。 总之，核心蛋白聚糖的全身过度表达可减少 ApoE(-/-) 小鼠动脉粥样硬化斑块中的炎症、甘油三酯和纤维化，从而减缓疾病进展。 (c) 2005 年，爱思唯尔爱尔兰有限公司出版。
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 x 10(9) plaque-forming units/mouse) containing human decorin gene Ad-Dcn) or beta-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-beta(1) (TGF-beta(1)) that resulted in reduced circulating free-TGF-beta(1).In conclusion, systemic overexpression of decorin reduces inflammation, triglycerides and fibrosis in atherosclerotic plaques of ApoE(-/-)mice resulting in slowing down of disease progression. (c) 2005 Published by Elsevier Ireland Ltd.