Transplanted perivascular adipose tissue accelerates injury-induced neointimal hyperplasia: role of monocyte chemoattractant protein-1.
Transplanted perivascular adipose tissue accelerates injury-induced neointimal hyperplasia: role of monocyte chemoattractant protein-1.
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DOI：
10.1161/atvbaha.114.303983
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Weintraub NL
中科院分区：
文献类型：
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作者：
Manka D;Chatterjee TK;Stoll LL;Basford JE;Konaniah ES;Srinivasan R;Bogdanov VY;Tang Y;Blomkalns AL;Hui DY;Weintraub NL
血管周围脂肪组织（PVAT）在肥胖期间膨胀，高度发炎，并与冠状动脉斑块负荷和心血管风险增加相关。我们检验了PVAT有助于血管对导丝损伤的反应的假设，并研究了潜在的机制。我们将喂食高脂饮食（HFD）的供体小鼠的胸主动脉PVAT移植到喂食HFD的受体LDLR−/−小鼠的颈动脉。移植后两周，进行金属丝损伤，两周后处死动物。进行免疫组织化学定量外膜巨噬细胞浸润和新生血管形成，以及新生内膜病变的组成和大小。移植的PVAT促进了新生内膜增生、外膜巨噬细胞浸润和外膜血管生成。PVAT移植动物中的大多数新生内膜细胞表达α-平滑肌肌动蛋白，与平滑肌表型一致。PVAT中MCP-1的缺失显著减弱了脂肪移植对新生内膜增生和外膜血管生成的影响，但不减弱外膜巨噬细胞浸润。血管周围脂肪细胞的条件培养基诱导单核细胞体外趋化和培养内皮细胞的血管生成反应。这些发现表明PVAT部分通过MCP-1依赖性机制促进血管对导丝损伤的反应。
Perivascular adipose tissue (PVAT) expands during obesity, is highly inflamed, and correlates with coronary plaque burden and increased cardiovascular risk. We tested the hypothesis that PVAT contributes to the vascular response to wire injury and investigated the underlying mechanisms. We transplanted thoracic aortic PVAT from donor mice fed a high-fat diet (HFD) to the carotid arteries of recipient HFD-fed LDLR−/− mice. Two weeks after transplantation, wire injury was performed, and animals were sacrificed two weeks later. Immunohistochemistry was performed to quantify adventitial macrophage infiltration and neovascularization, and neointimal lesion composition and size. Transplanted PVAT accelerated neointimal hyperplasia, adventitial macrophage infiltration and adventitial angiogenesis. The majority of neointimal cells in PVAT-transplanted animals expressed α-smooth muscle actin, consistent with smooth muscle phenotype. Deletion of MCP-1 in PVAT substantially attenuated the effects of fat transplantation on neointimal hyperplasia and adventitial angiogenesis, but not adventitial macrophage infiltration. Conditioned medium from perivascular adipocytes induced potent monocyte chemotaxis in vitro and angiogenic responses in cultured endothelial cells. These findings indicate that PVAT contributes to the vascular response to wire injury, in part through MCP-1-dependent mechanisms.