Genetics and mediators in pulmonary arterial hypertension.
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Journal: 2007/May - Clinics in Chest Medicine
ISSN: 0272-5231
Abstract:
Pulmonary arterial hypertension (PAH) is an uncommon disorder of the pulmonary vasculature characterized by remodeling of the smallest pulmonary arteries, leading to a progressive increase in pulmonary vascular resistance. Various forms of PAH exist, including familial (FPAH) and idiopathic (IPAH) forms and associated conditions. FPAH transmits as an autosomal dominant trait that exhibits genetic anticipation but also markedly reduced penetrance (20%). The primary genetic defect of FPAH, identifiable in more than 70% of cases of FPAH, is a mutation in the gene encoding bone morphogenetic protein receptor type 2 (BMPR2), a member of the transforming growth factor beta superfamily. The true prevalence of BMPR2 mutations in IPAH is unknown, with reports ranging from 10% to 40% of patients. The cause of the variable phenotypic expression of PAH among carriers of mutated BMPR2 genes and patients is unclear, and likely related to environmental and genetic modifiers of disease not yet fully elucidated. Although BMPR2-related pathways seem to be pivotal, many other mediator pathways participate in the pathogenesis of different forms of PAH and are being actively investigated, both independently and in combination. As understanding of the molecular basis of this devastating disease improves, opportunities for earlier diagnosis, additional therapeutic regimens, and perhaps disease prevention will emerge.
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Clin Chest Med 28(1): 43-viii
PMID: 17338927

Genetics and Mediators in Pulmonary Arterial Hypertension

Division of Pediatric Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, T-1217 Medical Center North, Nashville, TN 37232-2650, USA
Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, T-1217 Medical Center North, Nashville, TN 37232-2650, USA
Corresponding author. ude.tlibrednav@nitsua.cire (E.D. Austin).
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