Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF
Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF
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DOI：
10.1073/pnas.101564798
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发表时间：
2001-05-22
影响因子：
11.1
通讯作者：
Cao, YH
中科院分区：
文献类型：
--
作者：
Cao, RH;Brakenhielm, E;Cao, YH
大多数内分泌激素是在具有渗透性微血管的组织和器官中产生的，这些微血管可以提供过量的激素，通过血液循环输送到远端靶器官。在这里，我们研究瘦素（一种内分泌激素）是否诱导血管开窗和渗透性的形成，并在其他血管生成因子存在的情况下表征其血管生成特性。我们提供的证据表明瘦素诱导的新血管是有孔的。在生理条件下，瘦小鼠产生瘦素的脂肪组织中发现毛细血管开窗。相比之下，在缺乏瘦素的ob/ob小鼠的脂肪组织中没有检测到血管开窗。因此，瘦素在脂肪组织血管开窗的维持和调节中起着关键作用。皮内注射时，瘦素会引起快速的血管通透性反应。此外，瘦素可与成纤维细胞生长因子 (FCF)-2 和血管内皮生长因子 (VEGF) 这两种最有效且最常见的血管生成因子协同刺激血管生成。这些发现表明瘦素还有另一个新功能——增加血管通透性。
Most endocrine hormones are produced in tissues and organs with permeable microvessels that may provide an excess of hormones to be transported by the blood circulation to the distal target organ. Here, we investigate whether leptin, an endocrine hormone, induces the formation of vascular fenestrations and permeability, and we characterize its angiogenic property in the presence of other angiogenic factors. We provide evidence that leptin-induced new blood vessels are fenestrated. Under physiological conditions, capillary fenestrations are found in the leptin-producing adipose tissue in lean mice. In contrast, no vascular fenestrations were detected in the adipose tissue of leptin-deficient ob/ob mice. Thus, leptin plays a critical role in the maintenance and regulation of vascular fenestrations in the adipose tissue. Leptin induces a rapid vascular permeability response when administrated intradermally. Further, leptin synergistically stimulates angiogenesis with fibroblast growth factor (FCF)-2 and vascular endothelial growth factor (VEGF), the two most potent and commonly expressed angiogenic factors. These findings demonstrate that leptin has another new function-the increase of vascular permeability.