The effects of hypoxia on the cells of the pulmonary vasculature

Abstract

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.

Macrophage Migration Inhibitory Factor Mediates Hypoxia-Induced Pulmonary Hypertension

“…Chronic hypoxia induces structural changes to the pulmonary arteries including the appearance of SMC-like myofibroblasts expressing α-SMA, in previously nonmuscularized vessels. While hypoxia-induced remodeling is associated with medial hypertrophy, direct stimulation of SMC proliferation by hypoxia remains somewhat controversial (37). Although there are reports of hypoxia driven smooth muscle cell proliferation (38,39), several in vitro studies have shown that hypoxia does not directly increase SMC proliferation (40)(41)(42) or may actually decrease proliferation (43,44).…”

Time-Dependent Phenotypic and Contractile Changes of Pulmonary Artery in Chronic Hypoxia–Induced Pulmonary Hypertension

“…We speculate that chronic proliferative activity is involved in the thickening of the media wall and pulmonary arterial stenosis. Hypoxia could act on fibroblasts and endothelial cells to trigger PASMC proliferation (29). These adjacent cells with PASMCs can release many growth factors for PASMC proliferation such as PDGF, FGF-2, and EGF (30 -32).…”

Pulmonary Hypertension in the Course of Diffuse Parenchymal Lung Diseases—State of Art and Future Considerations

“…The established model of PH in the course of DPLD was the one related to vascular remodeling due to interstitial pathology and/or hypoxia [3]. Nevertheless, the presence of vascular pathology in the areas of minor interstitial lung disease, and the occurrence of PH in the early stage of disease in patients without substantial hypoxemia, indicate the more complex pathogenesis.…”