Macrophage infiltration into adipose tissue may promote angiogenesis for adipose tissue remodeling in obesity
Macrophage infiltration into adipose tissue may promote angiogenesis for adipose tissue remodeling in obesity
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DOI：
10.1152/ajpendo.90296.2008
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发表时间：
2008-08-01
影响因子：
5.1
通讯作者：
Ye, Jianping
中科院分区：
文献类型：
--
作者：
Pang, Can;Gao, Zhanguo;Ye, Jianping
巨噬细胞浸润到脂肪组织在肥胖中的生物学作用仍有待充分理解。我们推测巨噬细胞可能起到刺激脂肪组织血管生成的作用。通过测定巨噬细胞表达血管生成因子PDGF（血小板衍生生长因子）和PDGF调节内皮细胞管形成来检查这种可能性。这些数据表明，在ob/ob小鼠的脂肪组织中，内皮细胞密度降低。内皮细胞标志物CD 31蛋白和mRNA表达降低。这种减少与巨噬细胞浸润的增加有关。在肥胖小鼠中，血浆中PDGF浓度升高，脂肪组织中其mRNA表达增加。发现巨噬细胞是脂肪组织中PDGF的主要来源，因为巨噬细胞的缺失导致PDGF mRNA的显著减少。在细胞培养中，PDGF表达由缺氧诱导，并且由PDGF诱导内皮细胞的管形成。PDGF活性依赖于S6 K，因为内皮细胞中S6 K的抑制导致PDGF活性的抑制。我们的结论是，在响应减少血管密度，巨噬细胞可能表达PDGF在脂肪组织中，以促进毛细血管的形成肥胖。尽管PDGF水平在脂肪组织中升高，但其在血管生成中的活性依赖于足够内皮细胞的可用性。这项研究表明，在肥胖症的脂肪组织中的巨噬细胞的新功能。
The biological role of macrophage infiltration into adipose tissue in obesity remains to be fully understood. We hypothesize that macrophages may act to stimulate angiogenesis in the adipose tissue. This possibility was examined by determining macrophage expression of angiogenic factor PDGF (platelet-derived growth factor) and regulation of tube formation of endothelial cells by PDGF. The data suggest that endothelial cell density was reduced in the adipose tissue of ob/ob mice. Expression of endothelial marker CD31 was decreased in protein and mRNA. The reduction was associated with an increase in macrophage infiltration. In the obese mice, PDGF concentration was elevated in the plasma, and its mRNA expression was increased in adipose tissue. Macrophages were found to be a major source of PDGF in adipose tissue, as deletion of macrophages led to a significant reduction in PDGF mRNA. In cell culture, PDGF expression was induced by hypoxia, and tube formation of endothelial cells was induced by PDGF. The PDGF activity was dependent on S6K, as inhibition of S6K in endothelial cells led to inhibition of the PDGF activity. We conclude that, in response to the reduced vascular density, macrophages may express PDGF in adipose tissue to facilitate capillary formation in obesity. Although the PDGF level is elevated in adipose tissue, its activity in angiogenesis is dependent on the availability of sufficient endothelial cells. The study suggests a new function of macrophages in the adipose tissue in obesity.