Angiogenesis associated with visceral and subcutaneous adipose tissue in severe human obesity.

Angiogenesis associated with visceral and subcutaneous adipose tissue in severe human obesity.
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DOI:
10.2337/db07-1812
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发表时间:
2008-12
期刊:
影响因子:
7.7
通讯作者:
Larger E
Larger E
中科院分区:
医学1区
文献类型:
--
作者:
Ledoux S;Queguiner I;Msika S;Calderari S;Rufat P;Gasc JM;Corvol P;Larger E

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脂肪组织的扩张与其脉管系统的发育有关。然而,人类脂肪组织血管生成的调控尚未得到广泛研究。我们的目的是在体内模型中比较来自相同肥胖患者的皮下脂肪组织(SAT)和内脏脂肪组织(VAT)的血管生成。研究设计和方法-在减肥手术期间从36名肥胖患者(平均BMI 46.5 kg/m2)的内脏(VAT)和皮下(SAT)部位获得的脂肪组织样本,分层放置在鸡绒毛尿囊膜(CAM)上。SAT和VAT均表达血管生成因子,但血管内皮生长因子(VEGF)表达无显著差异。CAM上的脂肪组织层刺激血管生成。在39%的样本中,肉眼可检测到血管生成刺激,并伴有样本的吞噬,在59%的样本中通过血管造影术证实了这一点。CAM和脂肪组织血管之间的连接证明了免疫组织化学,与鸟类和人类内皮细胞的招聘。脂肪组织的血管生成能力与其定位(60%的SAT样本和61%的VAT样本中具有血管生成刺激)或脂肪细胞大小或在CAM上移植之前在脂肪样本中评估的炎性浸润无关。脂肪组织对血管生成的刺激几乎被特异性靶向人VEGF的贝伐单抗消除。结论:我们已经建立了一个模型来研究人体脂肪组织对血管生成的调节。该模型强调了VEGF在SAT和VAT中的血管生成中的作用。
OBJECTIVE—The expansion of adipose tissue is linked to the development of its vasculature. However, the regulation of adipose tissue angiogenesis in humans has not been extensively studied. Our aim was to compare the angiogenesis associated with subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from the same obese patients in an in vivo model. RESEARCH DESIGN AND METHODS—Adipose tissue samples from visceral (VAT) and subcutaneous (SAT) sites, obtained from 36 obese patients (mean BMI 46.5 kg/m2) during bariatric surgery, were layered on chick chorioallantoïc membrane (CAM). RESULTS—Both SAT and VAT expressed angiogenic factors without significant difference for vascular endothelial growth factor (VEGF) expression. Adipose tissue layered on CAM stimulated angiogenesis. Angiogenic stimulation was macroscopically detectable, with engulfment of the samples, in 39% and was evidenced by angiography in 59% of the samples. A connection between CAM and adipose tissue vessels was evidenced by immunohistochemistry, with recruitment of both avian and human endothelial cells. The angiogenic potency of adipose tissue was not related to its localization (with an angiogenic stimulation in 60% of SAT samples and 61% of VAT samples) or to adipocyte size or inflammatory infiltrate assessed in adipose samples before the graft on CAM. Stimulation of angiogenesis by adipose tissue was nearly abolished by bevacizumab, which specifically targets human VEGF. CONCLUSIONS—We have established a model to study the regulation of angiogenesis by human adipose tissue. This model highlighted the role of VEGF in angiogenesis in both SAT and VAT.