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.
Cao
R
R
Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Center for Genomic Research, Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden.
Brakenhielm
E
E
Wahlestedt
C
C
Thyberg
J
J
Cao
Y
Y
D000273:Adipose Tissue; D000818:Animals; D002196:Capillaries / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000098:blood supply / Q000187:drug effects / Q000648:ultrastructure; D016510:Corneal Neovascularization; D004357:Drug Synergism; D016228:Endothelial Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D020738:Leptin / Q000008:administration & dosage / Q000502:physiology*; D008222:Lymphokines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D020738:Leptin; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2