Leptin Induces Vascular Permeability and Synergistically Stimulates Angiogenesis with FGF-2 and VEGF

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 11; pp. 6390 - 6395
• Main Authors: Cao, Renhai, Brakenhielm, Ebba, Wahlestedt, Claes, Thyberg, Johan, Cao, Yihai
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 22.05.2001; National Acad Sciences; The National Academy of Sciences
• Subjects: Adipose Tissue; Adipose tissues; Angiogenesis; Animals; Biological Sciences; Blood vessels; Capillaries; Capillaries - cytology; Capillary Permeability - drug effects; Capillary Permeability - physiology; Cattle; Cell Division - drug effects; Cells; Cells, Cultured; Cornea; Cornea - blood supply; Cornea - drug effects; Cornea - ultrastructure; Corneal Neovascularization; Drug Synergism; Endothelial cells; Endothelial Growth Factors - administration & dosage; Endothelial Growth Factors - pharmacology; Endothelium, Vascular - cytology; Female; Fibroblast Growth Factor 2 - administration & dosage; Fibroblast Growth Factor 2 - pharmacology; Hormones; Humans; Leptin - administration & dosage; Leptin - physiology; Lymphokines - administration & dosage; Lymphokines - pharmacology; Male; Medicin och hälsovetenskap; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Obese; Microvessels; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Obesity; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.101564798

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.