Medial and adventitial macrophages are associated with expansive atherosclerotic remodeling in rabbit femoral artery
Medial and adventitial macrophages are associated with expansive atherosclerotic remodeling in rabbit femoral artery
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DOI：
10.14670/hh-23.127
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发表时间：
2008-02-01
影响因子：
2
通讯作者：
Asada, Y.
中科院分区：
文献类型：
--
作者：
Yamashita, A.;Shoji, K.;Asada, Y.
扩张性血管重塑被认为是易损斑块的一个特征。尽管炎症在动脉粥样硬化病变的中膜和外膜中表达上调，但其对扩张性重塑的作用尚不清楚。我们在正常和高脂血症兔的股动脉损伤中研究了这一问题，这些兔分别以常规饮食(CD组，n=20)和0.5%胆固醇饮食(CHD组，n=20)喂养。球囊损伤股动脉4周后，我们检测了血管壁的改变，巨噬细胞和基质金属蛋白酶(MMPs)-1、-2、-9和细胞外基质的定位。冠心病组和冠心病组均有明显的新生内膜形成和管腔狭窄，而扩张性重构仅见于冠心病组。MMP1、MMP2和MMP9免疫阳性面积不仅在冠心病组新生内膜，而且在受损动脉壁的中膜和/或外膜均大于冠心病组。冠心病组损伤动脉壁内含有平滑肌细胞、弹性蛋白和胶原的面积较小。MMP1、MMP2和MMP9主要定位于浸润性巨噬细胞。MMP2在SMC和外膜成纤维细胞也有表达。冠心病组损伤动脉VASA血管密度明显高于冠心病组。这些结果提示，中膜和外膜巨噬细胞通过降解细胞外基质和减少SMC在扩张性动脉粥样硬化重塑中起重要作用。
Expansive vascular remodeling is considered a feature of vulnerable plaques. Although inflammation is upregulated in the media and adventitia of atherosclerotic lesions, its contribution to expansive remodeling is unclear. We investigated this issue in injured femoral arteries of normo- and hyperlipidemic rabbits fed with a conventional (CD group; n=20) or a 0.5% cholesterol (ChD group; n=20) diet. Four weeks after balloon injury of the femoral arteries, we examined vascular wall alterations, localization of macrophages and matrix metalloproteases (MMP)- 1, - 2, - 9, and extracellular matrix. Neointimal formation with luminal stenosis was evident in both groups, while expansive remodeling was observed only in the ChD group. Areas immunopositive for macrophages, MMP- 1, - 2 and - 9 were larger not only in the neointima, but also in the media and/or adventitia in the injured arterial walls of the ChD, than in the CD group. Areas containing smooth muscle cells (SMCs), elastin and collagen were smaller in the injured arterial walls of the ChD group. MMP- 1, - 2 and - 9 were mainly localized in infiltrating macrophages. MMP- 2 was also found in SMCs and adventitial fibroblasts. Vasa vasorum density was significantly increased in injured arteries of ChD group than in those of CD group. These results suggest that macrophages in the media and adventitia play an important role in expansive atherosclerotic remodeling via extracellular matrix degradation and SMC reduction.