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Related Experiment Videos

Endothelial cell responses to hypoxic stress.

D V Faller1

  • 1Cancer Research Center, Boston University School of Medicine, MA 02118, USA. dfaller@bu.edu

Clinical and Experimental Pharmacology & Physiology
|February 23, 1999
PubMed
Summary

Cellular responses to low oxygen (hypoxia) involve gene expression changes affecting vascular tone and tissue remodeling. Nitric oxide (NO) signaling interacts with hypoxia, influencing physiological and pathological outcomes in diseases like atherosclerosis.

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Area of Science:

  • Cellular and Molecular Biology
  • Physiology
  • Pathophysiology

Background:

  • Environmental oxygen tension influences cellular physiology through differential gene expression.
  • Low oxygen tension (hypoxia) significantly impacts endothelial cell function, regulating genes involved in vascular tone and tissue remodeling.
  • Hypoxia affects the transcription of vasoconstrictors, mitogens, matrix proteins, and vasodilators like nitric oxide (NO).

Purpose of the Study:

  • To elucidate the mechanisms by which oxygen tension alters gene expression in endothelial cells.
  • To understand the interplay between hypoxia and nitric oxide (NO) signaling in vascular regulation.
  • To explain how differential responses to hypoxia contribute to various pathophysiological conditions.

Main Methods:

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  • Analysis of gene expression changes in endothelial cells under varying oxygen tensions.
  • Investigation of signaling pathways involving transcription factors (AP-1, NF-kappa B, HIF-1) and a novel oxygen sensor.
  • Examination of the modulatory effects of nitric oxide (NO) on hypoxia-induced gene expression.
  • Main Results:

    • Hypoxia induces genes for vasoconstrictors (e.g., PDGF-B, endothelin-1, VEGF) and matrix remodeling (e.g., MMP-9), while inhibiting vasodilators (e.g., eNOS).
    • Oxygen sensing involves a haem-containing sensor that modulates transcription factor activity.
    • Nitric oxide (NO) and hypoxia signaling pathways are interconnected, with NO capable of reversing hypoxia-induced vasoconstriction.
    • Short-term hypoxia causes reversible vascular tone changes, whereas chronic hypoxia leads to irreversible tissue remodeling, smooth muscle proliferation, and fibrosis.

    Conclusions:

    • Endothelial cells exhibit distinct responses to hypoxia based on duration and severity, leading to either physiological modulation or pathological tissue remodeling.
    • The interaction between hypoxia and nitric oxide (NO) signaling is crucial for vascular homeostasis.
    • Differential responses to hypoxia contribute to the pathophysiology of diseases such as atherosclerosis, pulmonary hypertension, and systemic sclerosis.