PDGF signaling in pulmonary arterial hypertension

J Clin Invest. 2005 Oct;115(10):2691-4. doi: 10.1172/JCI26593.

Abstract

The pathobiology of pulmonary arterial hypertension (PAH) includes endothelial cell dysfunction and proliferation and migration of VSMCs. As PDGF has been implicated in these processes, Schermuly et al. hypothesized that altered PDGF signaling may be involved in the vascular remodeling observed in PAH. To explore this notion further, the authors evaluated the effects of the PDGF receptor inhibitor STI571 in 2 different animal models of pulmonary hypertension. In both models, after development of pulmonary vascular disease, administration of STI571 reversed pulmonary vascular changes. These studies provide preclinical proof of concept for the clinical development of a PDGF inhibitor as a targeted therapy for PAH patients.

Publication types

  • Comment
  • Review

MeSH terms

  • Animals
  • Benzamides
  • Disease Models, Animal
  • Humans
  • Hypertension, Pulmonary / drug therapy
  • Hypertension, Pulmonary / metabolism*
  • Imatinib Mesylate
  • Piperazines / therapeutic use
  • Platelet-Derived Growth Factor / antagonists & inhibitors
  • Platelet-Derived Growth Factor / metabolism*
  • Protein Kinase Inhibitors / therapeutic use
  • Pulmonary Artery / metabolism*
  • Pyrimidines / therapeutic use
  • Receptors, Platelet-Derived Growth Factor / metabolism

Substances

  • Benzamides
  • Piperazines
  • Platelet-Derived Growth Factor
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Receptors, Platelet-Derived Growth Factor