Chronic pulmonary hypoxia causes pulmonary hypertension, which results from a sustained increase in pulmonary vascular resistance, a response to hypoxia that is not seen in other vascular beds. The changes in the vasculature that accompany this include arterial remodelling, an altered contractile state and angiogenesis (3). These pulmonary specific responses suggest that there are genes whose expression is altered selectively in the lung in response to alveolar hypoxia, controlled by specific transcriptional mechanisms (4). The bone morphogenetic antagonist (BMP), gremlin 1, is selectively upregulated in the hypoxic lung in vivo, but not in other organs (1, 2). This gene is of particular interest because it has previously been found that heterozygous BMP receptor mutations assoicated with reduced receptor signalling were the underlying defect in families with a rare heritable form of pulmonary arterial hypertension. BMP signaling is also reduced in hypoxic pulmonary hypertension. Evidence for the role of the BMP antagonists in hypoxic pulmonary hypertension and in human disease will be reviewed, the transcriptional mechanisms underlying their lung selective hypoxic regulation and their actions on vascular structure and function.

References: 

1. Costello et al. Am J Resp Cell Mol Biol 42: 517–523, 2010.

2. Costello et al. Am J Physiol Lung Cell Mol Physiol 295: L272–284, 2008.

3. Hyvelin J-M et al. Circ Res 97: 185–191, 2005.

4. Leonard et al. Am J Respir Crit Care Med 178: 977–983, 2008.