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Copyright ©ERS Journals Ltd 2002
Pathobiology of pulmonary arterial hypertension
1 INSERM U492 and Dept of Physiology, Hôpital H. Mondor, AP-HP, Créteil, France. 2 Dept of Medicine, University of Cambridge, Addenbrooke's and Papworth Hospitals, Cambridge, UK. 3 Laboratory of Physiology, Erasme University hospital, Brussels, Belgium
CORRESPONDENCE: S. Adnot, INSERM U492, Département de Physiologie, Faculté de Médecine de Créteil, 94010 Créteil, France. Fax: 33 148981777. E-mail: serge.adnot@creteil.inserm.fr
Keywords: bone morphogenic receptor-II, extracellular matrix remodelling, primary pulmonary hypertension, pulmonary vascular remodelling, serotonin transporter, smooth muscle
Received: September 2, 2002
Accepted September 9, 2002
Abstract
Recent years have witnessed important advances in the understanding of the pathophysiology of primary pulmonary hypertension (PPH). Both genetic and mechanistic studies have succeeded in identifying new molecular pathways relevant to the process of pulmonary vascular remodelling, which underlies PPH.
Mutations in the type II bone morphogenetic protein (BMP) receptor (BMPR)-II are now considered to be the genetic basis for familial PPH and
As PPH does not develop in all subjects with BMPR-II mutations, environmental or associated genetic factors may play a crucial role. Among these, the finding of an association between PPH and the L-allelic variant of the serotonin transporter (5-HTT) gene indicates that 5-HTT, which controls smooth muscle hyperplasia, probably contributes to susceptibility to PPH or is an important modifier of the PPH phenotype.
Recognition of these molecular pathways should provide insight into the pathogenesis not only of primary pulmonary hypertension, but also of secondary forms of pulmonary hypertension. This should soon lead to the development of new and more selective therapeutic approaches to pulmonary hypertension.
30% of cases of sporadic PPH. The identification of the relevance of the BMP pathway to the aetiology of PPH now raises many questions about the link between the BMPR-II mutant genotype and the PPH phenotype.
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