Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF

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 (FGF)-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.

多数内分泌激素由具有通透性微血管的组织与器官分泌，此类微血管可将过量激素经血液循环运送至远端靶器官。本研究旨在探究内分泌激素瘦素（leptin）是否可诱导血管窗孔（vascular fenestrations）形成并提升血管通透性，并在其他血管生成因子存在的条件下，表征其血管生成特性。本研究证实，瘦素诱导生成的新生血管带有窗孔结构。在生理状态下，瘦型小鼠体内分泌瘦素的脂肪组织中可观察到毛细血管窗孔；与之相反，瘦素缺陷型ob/ob小鼠的脂肪组织中未检测到血管窗孔。由此可见，瘦素在维持并调控脂肪组织的血管窗孔结构中发挥关键作用。经皮内注射给药后，瘦素可快速引发血管通透性应答。此外，瘦素可与两种最强效且普遍表达的血管生成因子——成纤维细胞生长因子2（fibroblast growth factor (FGF)-2）与血管内皮生长因子（vascular endothelial growth factor (VEGF)）——协同促进血管生成。上述研究结果表明，瘦素具备一项全新功能：提升血管通透性。