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Cited by 50High Altitude and HypoxiaPregnancy and preeclampsia studiesCancer, Hypoxia, and Metabolism

Greater vascularity, lowered HIF-1/DNA binding, and elevated GSH as markers of adaptation to in vivo chronic hypoxia

Tissot van Patot, M. C., Bendrick-Peart, J., Beckey, V. E., Serkova, N., Zwerdlinger, L.·2004·American Journal of Physiology-Lung Cellular and Molecular Physiology
DOI 10.1152/ajplung.00203.2003
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Abstract

Vascularity is increased in placentas from high- compared with low-altitude pregnancies. An angiogenic response to hypoxia may protect an organ from further hypoxic insult by increasing blood flow and oxygen delivery to the tissue. We hypothesized that increased placental vascularity is sufficient to adapt to high altitude. Therefore, indexes of hypoxic stress would not be present in placentas from successful high-altitude pregnancies. Full-thickness placental biopsies were 1) collected and frozen in liquid nitrogen within 5 min of placental delivery and 2) fixed in formalin for stereologic analyses at high (3,100 m, n = 10) and low (1,600 m, n = 10) altitude. Hypoxia-inducible transcription factor (HIF-1) activity was analyzed by ELISA. Western blot analyses were used to evaluate HIF-1α, HIF-1β, HIF-2α, von Hippel-Lindau protein, VEGF, Flt-1, enolase, and GAPDH. Magnetic resonance spectroscopy was used to evaluate endogenous metabolism. The ratio of placental capillary surface density to villous surface density was 70% greater at high compared with low altitude. HIF-1 activity and HIF-1-associated proteins were unchanged in placentas from high- vs. low-altitude pregnancies. Placental expression of HIF-1-mediated proteins VEGF, Flt-1, enolase, and GAPDH were unchanged at high vs. low altitude. Succinate, GSH, phosphomonoesters, and ADP were elevated in placenta from high compared with low altitude. Placentas from uncomplicated high-altitude pregnancies have greater vascularity and no indication of significant hypoxic stress at term compared with placentas from low altitude.

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Crossref · 10.1152/ajplung.00203.2003

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  • The downregulation of complex I and III may explain the reduced HIF-binding reported in high-altitude placentas.

    “This may explain the reduced HIF-binding reported in these placentas (533).”

    From Placental Origins of Chronic Disease (2016) · cites this paper as [533]

  • Another study of placentas from the same high-altitude region found enhanced vascularization, consistent with a hypoxic response, but HIF-DNA binding was less than in low-altitude controls.

    “Another study of placentas from the same region found enhanced vascularization, consistent with a hypoxic response, but paradoxically HIF-DNA binding was less than in the lowaltitude controls (533).”

    From Placental Origins of Chronic Disease (2016) · cites this paper as [533]

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Authors
Tissot van Patot, M. C., Bendrick-Peart, J., Beckey, V. E., Serkova, N., & Zwerdlinger, L.
ORCID
Serkova, N.
Venue
American Journal of Physiology-Lung Cellular and Molecular Physiology
Publisher
American Physiological Society
Published
2004-09
Volume
287
Issue
3
Pages
L525-L532
ISSN
  • 1040-0605 (ISSN-L)
  • 1522-1504
DOI
10.1152/ajplung.00203.2003
OpenAlex
W1885960149
Cited by
50
References
35
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 2 · 2012: 3
FWCI
1.78
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Lung Cellular and Molecular Physiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › High Altitude and Hypoxia
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
placental vascularization, chronic hypoxia, high altitude, HIF-1, hypoxia-inducible factor, glutathione, angiogenesis, vascular endothelial growth factor, Flt-1, enolase, von Hippel-Lindau protein, placental adaptation, succinic acid, endogenous metabolism, term pregnancy
MeSH terms
Endothelial PAS Domain-Containing Protein 1, Adaptation, Physiological, Altitude, Hypoxia, Chronic Disease, Female, Glutathione, Humans, Placenta, Pregnancy, Pregnancy Complications, Transcription Factors, Biomarkers, Trans-Activators, Vascular Endothelial Growth Factor Receptor-1, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit

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