Cited by 447Angiogenesis and VEGF in CancerBarrier Structure and Function StudiesAdipokines, Inflammation, and Metabolic Diseases

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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

DOI 10.1073/pnas.101564798PMC PMC33478

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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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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
ORCID: Wahlestedt, Claes
Cao, Yihai
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2001-05-08
Volume: 98
Issue: 11
Pages: 6390-6395
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.101564798
PMC: PMC33478
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: green
europepmc.org
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 › Endocrinology, Diabetes and Metabolism › 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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Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF

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