Cited by 448Angiogenesis and VEGF in CancerBarrier Structure and Function StudiesAdipokines, Inflammation, and Metabolic Diseases

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

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Cao, Renhai, Brakenhielm, Ebba, Wahlestedt, Claes, Thyberg, Johan, Cao, Yihai·2001·Proceedings of the National Academy of Sciences

Abstract

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.

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Crossref · 10.1073/pnas.101564798

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  • Adipose tissue secretes several adipokines and endogenous angiogenesis inhibitors that modulate new blood vessel formation, including adiponectin, leptin, resistin, visfatin/thrombospondin 1, and plasminogen activator inhibitor.

    “In addition to authentic angiogenic factors, AT secretes several important adipokines and endogenous angiogenesis inhibitors to modulate the balance of new blood vessel formation, including adiponectin (36,37), leptin (34), resistin (38), visfatin/thrombospondin 1 (39), and plasminogen activator inhibitor (40).”

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Authors
Cao, R., Brakenhielm, E., Wahlestedt, C., Thyberg, J., & Cao, Y.
Affiliations
  • Karolinska Institutet (SE)
  • 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
Venue
Proceedings of the National Academy of Sciences
Published
2001-05-08
Volume
98
Issue
11
Pages
6390-6395
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2111796479
Cited by
446
References
29
Citations by year
2026: 5 · 2025: 10 · 2024: 7 · 2023: 12 · 2022: 22 · 2021: 17 · 2020: 19 · 2019: 19 · 2018: 14 · 2017: 23 · 2016: 17 · 2015: 17 · 2014: 18 · 2013: 40 · 2012: 24
FWCI
6.17
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
leptin, vascular permeability, angiogenesis, FGF2, vascular endothelial growth factor, adipose tissue, ob/ob mice, hormone transport
MeSH terms
Adipose Tissue, Animals, Capillaries, Capillary Permeability, Cattle, Cell Division, Cells, Cultured, Cornea, Drug Synergism, Endothelium, Vascular, Female, Humans, Lymphokines, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Obese, Fibroblast Growth Factor 2, Endothelial Growth Factors, Corneal Neovascularization, Neovascularization, Physiologic, Leptin, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Mice

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