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Cited by 385Barrier Structure and Function StudiesAngiogenesis and VEGF in CancerGrowth Hormone and Insulin-like Growth Factors

Insulin-like growth factor I is required for vessel remodeling in the adult brain.

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Lopez-Lopez, C., LeRoith, D., Torres-Aleman, I.·2004·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0400337101PMC PMC470760
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Abstract

Although vascular dysfunction is a major suspect in the etiology of several important neurodegenerative diseases, the signals involved in vessel homeostasis in the brain are still poorly understood. We have determined whether insulin-like growth factor I (IGF-I), a wide-spectrum growth factor with angiogenic actions, participates in vascular remodeling in the adult brain. IGF-I induces the growth of cultured brain endothelial cells through hypoxiainducible factor 1 alpha and vascular endothelial growth factor, a canonical angiogenic pathway. Furthermore, the systemic injection of IGF-I in adult mice increases brain vessel density. Physical exercise that stimulates widespread brain vessel growth in normal mice fails to do so in mice with low serum IGF-I. Brain injury that stimulates angiogenesis at the injury site also requires IGF-I to promote perilesion vessel growth, because blockade of IGF-I input by an anti-IGF-I abrogates vascular growth at the injury site. Thus, IGF-I participates in vessel remodeling in the adult brain. Low serum/brain IGF-I levels that are associated with old age and with several neurodegenerative diseases may be related to an increased risk of vascular dysfunction.

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  • Both exercise and systemic infusion of IGF-1 increase new and survivability of BrdU+ cells in the hippocampus, likely signaling through IGF receptors on the luminal side of the brain.

    “and both exercise and systemic infusion of IGF-1 increases new and survivability of BrdU+ cells in the hippocampus (323, 521), likely signaling through IGF-receptors located on the luminal side of the brain (323).”

    From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [323]

  • In culture, IGF stimulates VEGF via a HIF mechanism.

    “In culture, IGF stimulates VEGF via a HIF mechanism (323).”

    From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [323]

  • IGF-1 supports alterations in vascularization induced by AE and promotes the proliferation and survival of newborn neural cells.

    “Similarly, IGF-1 is known to support alterations in vascularization that are induced by AE (Lopez-Lopez et al., 2004) and promotes the proliferation and survival of newborn neural cells (Gomez-Pinilla and Hillman, 2013).”

    From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Lopez-Lopez et al., 2004

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Authors
Lopez-Lopez, C., LeRoith, D., & Torres-Aleman, I.
Affiliations
  • Laboratory of Neuroendocrinology, Cajal Institute, Consejo Superior de Investigaciones Cientifícas, 28002 Madrid, Spain; and Clinical Endocrinology Branch, National Institutes of Health, Bethesda, MD 20892
  • National Institutes of Health (US)
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2004-06-21
Volume
101
Issue
26
Pages
9833-9838
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0400337101
PMC
PMC470760
OpenAlex
W2122104062
Cited by
385
References
37
Citations by year
2026: 3 · 2025: 13 · 2024: 8 · 2023: 22 · 2022: 11 · 2021: 21 · 2020: 16 · 2019: 18 · 2018: 15 · 2017: 20 · 2016: 24 · 2015: 20 · 2014: 17 · 2013: 16 · 2012: 29
FWCI
10.62
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)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
insulin-like growth factor I, angiogenesis, hypoxia-inducible factor-1α, vascular endothelial growth factor, brain endothelial cells, physical activity, brain injury, neurodegenerative diseases, vascular dysfunction, aging
MeSH terms
Aging, Animals, Antibodies, Brain, Brain Injuries, Cell Division, Cells, Cultured, Insulin-Like Growth Factor I, Male, Mice, Inbred C57BL, Mutation, Physical Conditioning, Animal, Rats, Wistar, Neovascularization, Physiologic, Endothelial Cells, Serum, Mice, Rats

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