Manka David, Chatterjee Tapan K, Stoll Lynn L, Basford Joshua E, Konaniah Eddy S, Srinivasan Ramprasad, Bogdanov Vladimir Y, Tang Yaoliang, Blomkalns Andra L, Hui David Y, Weintraub Neal L
From the Department of Internal Medicine, Division of Cardiovascular Diseases (D.M.), Department of Pathology and Laboratory Medicine (J.E.B., E.S.K., D.Y.H.), Department of Internal Medicine, Division of Hematology/Oncology (R.S., V.Y.B.), and Department of Emergency Medicine (A.L.B.), University of Cincinnati, OH; Department of Internal Medicine, Vascular Biology Center, Georgia Regents University, Augusta (T.K.C., Y.T., N.L.W.); and Department of Emergency Medicine, University of Iowa, Iowa City (retired) (L.L.S.).
Arterioscler Thromb Vasc Biol. 2014 Aug;34(8):1723-30. doi: 10.1161/ATVBAHA.114.303983. Epub 2014 Jun 19.
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 to the carotid arteries of recipient high-fat diet-fed low-density lipoprotein receptor knockout mice. Two weeks after transplantation, wire injury was performed, and animals were euthanized 2 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 monocyte chemoattractant protein-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 monocyte chemoattractant protein-1-dependent mechanisms.
血管周围脂肪组织（PVAT）在肥胖过程中会扩张，具有高度炎症反应，且与冠状动脉斑块负荷及心血管风险增加相关。我们检验了PVAT促成血管对钢丝损伤反应的假说，并研究了其潜在机制。
我们将高脂饮食喂养的供体小鼠的胸主动脉PVAT移植到高脂饮食喂养的低密度脂蛋白受体敲除受体小鼠的颈动脉。移植两周后，进行钢丝损伤，2周后对动物实施安乐死。进行免疫组织化学以量化外膜巨噬细胞浸润、新生血管形成以及内膜病变的组成和大小。移植的PVAT加速了内膜增生、外膜巨噬细胞浸润和外膜血管生成。PVAT移植动物的大多数内膜细胞表达α平滑肌肌动蛋白，与平滑肌表型一致。PVAT中单核细胞趋化蛋白-1的缺失显著减弱了脂肪移植对内膜增生和外膜血管生成的影响，但对外膜巨噬细胞浸润无影响。血管周围脂肪细胞的条件培养基在体外诱导了强烈的单核细胞趋化作用，并在培养的内皮细胞中诱导了血管生成反应。
这些发现表明，PVAT促成了血管对钢丝损伤的反应，部分是通过单核细胞趋化蛋白-1依赖性机制实现的。
