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Angiogenesis in the Ischemic Rat Lung
07:36

Angiogenesis in the Ischemic Rat Lung

Published on: February 8, 2013

Hypoxia-induced mitogenic factor has proangiogenic and proinflammatory effects in the lung via VEGF and VEGF

Kazuyo Yamaji-Kegan1, Qingning Su, Daniel J Angelini

  • 1Department of Anesthesiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|August 8, 2006
PubMed

Insights

Hypoxia-induced mitogenic factor (HIMF) drives pulmonary vascular remodeling by promoting cell growth and inflammation. Blocking VEGF receptor-2 (VEGFR2) significantly reduces these HIMF-induced effects, suggesting a therapeutic target.

Area of Science:

  • Pulmonary Hypertension Research
  • Molecular Biology
  • Immunology

Background:

  • Hypoxia-induced pulmonary hypertension (HPH) involves complex molecular mechanisms.
  • Hypoxia-induced mitogenic factor (HIMF), also known as FIZZ1 and RELMalpha, is upregulated in HPH.
  • The specific roles of HIMF in pulmonary vascular remodeling remain unclear.

Purpose of the Study:

  • To elucidate the mechanisms by which HIMF contributes to pulmonary vascular remodeling.
  • To investigate HIMF's effects on pulmonary endothelial cells and inflammatory cells.
  • To assess the role of VEGF receptor-2 (VEGFR2) in HIMF-mediated processes.

Main Methods:

  • In vitro studies on pulmonary endothelial cells and murine monocyte/macrophage cells.
  • In vivo Matrigel plug assays with VEGFR2 blockade.
  • Ex vivo lung cell cultures and intravenous HIMF injection models.
  • VEGFR2 neutralization experiments.

Main Results:

  • HIMF promotes pulmonary endothelial cell proliferation, migration, and VEGF/MCP-1 production.
  • HIMF induces reactive oxygen species in monocytes/macrophages.
  • VEGFR2 blockade significantly inhibits HIMF-induced angiogenesis and inflammatory cell infiltration.
  • HIMF stimulates lung resident cells to produce VEGF, MCP-1, and SDF-1, with VEGFR2 neutralization partially blocking this.

Conclusions:

  • HIMF plays a critical role in pulmonary inflammation and angiogenesis.
  • HIMF-mediated pulmonary vascular remodeling involves VEGFR2 signaling.
  • Targeting HIMF or VEGFR2 may offer therapeutic strategies for HPH.

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