The effects of hypoxia on the cells of the pulmonary vasculature

O. Pak, A. Aldashev, D. Welsh, A. Peacock*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

160 Citations (Scopus)


Pulmonary hypertension is associated with remodelling of pulmonary vessels. Chronic hypoxia is a common cause of pulmonary hypertension and pulmonary vascular remodelling. Vascular remodelling is characterised largely by fibroblast, smooth muscle and endothelial cell proliferation, which results in lumen obliteration. Chronic hypoxia elicits expression of mitogens, growth factors and cytokines by fibroblasts and endothelial cells, and also the suppression of endothelial nitric oxide synthase. Although hypoxic pulmonary vascular remodelling is associated with medial hypertrophy, many in vitro studies have found that hypoxia does not lead to a direct increase in smooth muscle cell proliferation. This paradox is not well understood and this review aims to examine the various reasons why this might be so. The present authors reviewed data from in vitro studies and also considered whether hypoxia could act on adjacent cells such as fibroblasts and endothelial cells to trigger smooth muscle cell proliferation. It is possible that hypoxia is sensed by fibroblasts, endothelial cells, or both, and relayed to adjacent pulmonary artery smooth muscle cells by intercellular signalling, causing proliferation. The present article reviews the data from in vitro studies of hypoxia on the three cellular components of the pulmonary vascular wall, namely endothelial cells, smooth muscle cells and fibroblasts.

Original languageEnglish
Pages (from-to)364-372
Number of pages9
JournalEuropean Respiratory Journal
Issue number2
Early online date31 Jul 2007
Publication statusPublished - Aug 2007


  • endothelial cells
  • fibroblast
  • hypoxia
  • proliferation
  • remodelling
  • smooth muscle cells

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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