Hypoxia does neither stimulate pulmonary artery endothelial cell proliferation in mice and rats with pulmonary hypertension and vascular remodeling nor in human pulmonary artery endothelial cells

J Vasc Res. 2011;48(6):465-75. doi: 10.1159/000327005. Epub 2011 Jun 17.

Abstract

Background: Hypoxia results in pulmonary hypertension and vascular remodeling due to induction of pulmonary artery cell proliferation. Besides pulmonary artery smooth muscle cells, pulmonary artery endothelial cells (PAECs) are also involved in the development of pulmonary hypertension, but the effect of hypoxia on PAEC proliferation has not been completely understood.

Methods: We investigated PAEC proliferation in mice and rats with hypoxia-induced pulmonary hypertension and vascular remodeling as well as in human PAECs under hypoxia.

Results and conclusion: We did not find significant PAEC proliferation in chronically hypoxic rats or mice. There was a slight decrease in proliferation in mice and rats with pulmonary hypertension and vascular remodeling. We also did not find significant human PAEC proliferation and cell cycle progression under different levels of oxygen (1, 2, 3, 5 and 10%) for one day, although the same conditions of hypoxia induced significant proliferation and cell cycle progression in pulmonary artery smooth muscle cells and pulmonary artery fibroblasts. Exposure to hypoxia for 7 days also did not increase PAEC proliferation. These results demonstrated that hypoxia alone is not a stimulus to PAEC proliferation in vivo and in vitro. The present study provides a novel role for PAECs in hypoxia-induced pulmonary hypertension and vascular remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / physiology
  • Cell Movement / physiology
  • Cell Proliferation
  • Cells, Cultured
  • Endothelial Cells / cytology*
  • Endothelial Cells / physiology
  • Humans
  • Hypertension, Pulmonary / pathology
  • Hypertension, Pulmonary / physiopathology*
  • Hypoxia / pathology
  • Hypoxia / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / physiology
  • Oxygen / pharmacology
  • Pulmonary Artery / cytology*
  • Pulmonary Circulation / physiology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Oxygen