Molecular mechanisms of pulmonary arterial hypertension: role of mutations in the bone morphogenetic protein type II receptor

Chest. 2008 Dec;134(6):1271-1277. doi: 10.1378/chest.08-1341.

Abstract

Pulmonary arterial hypertension (PAH) is characterized by abnormal remodeling of small, peripheral resistance vessels in the lung involving proliferation and migration of vascular smooth muscle, endothelial cell and fibroblasts. The increase in pulmonary vascular resistance leads to right heart failure, and, without treatment, death occurs within 3 years of diagnosis. The etiology of PAH is multifactorial. In some patients, there is a major genetic predisposition in the form of heterozygous germline mutations in a transforming growth factor-beta superfamily receptor, the bone morphogenetic type II receptor (BMPR-II). In addition, it is likely that additional factors, such as inflammation, are important to manifest disease. The currently available treatments for PAH were developed mainly as vasodilators, and although they improve symptoms they have limited impact on survival. This review examines the role of the BMPR-II signaling pathway in the process of pulmonary vascular remodeling. We discuss the ways in which manipulation of BMPR-II signaling might be targeted with the aim of preventing or reversing vascular remodeling and improving survival in patients with PAH.

Publication types

  • Review

MeSH terms

  • Bone Morphogenetic Protein Receptors, Type II / genetics*
  • Humans
  • Hypertension, Pulmonary / genetics*
  • Hypertension, Pulmonary / pathology
  • Hypertension, Pulmonary / prevention & control
  • Mutation / genetics*
  • Signal Transduction / physiology
  • Transforming Growth Factor beta / physiology
  • Vascular Resistance / genetics

Substances

  • Transforming Growth Factor beta
  • Bone Morphogenetic Protein Receptors, Type II