Targeting PDGF pathway in pulmonary arterial hypertension

Expert Opin Ther Targets. 2012 Nov;16(11):1055-63. doi: 10.1517/14728222.2012.719500. Epub 2012 Aug 27.

Abstract

Introduction: Pulmonary arterial hypertension (PAH) encompasses a rare potentially lethal group of diseases characterized by vasoconstriction, in situ thrombosis and vascular remodeling. Most of the existing therapies including endothelin receptor antagonists, prostacyclin and derivatives, or phsophodiesterase-5 inhibitors tackle mainly the endothelial dysfunction, leaving the remodeling suboptimally inhibited. This explains the disease progression that occurs even with combined therapies and the need for other therapies able to adequately inhibit the vascular remodeling.

Areas covered: Platelet-derived growth factor (PDGF) signaling pathway was demonstrated to be involved in the vascular remodeling in PAH, and therefore, it might be a desirable therapeutic target in this setting. This review discusses the pathogenic role of this pathway in PAH and its potential inhibitory approaches, focusing on imatinib as well as on the existing preclinical data on this compound.

Expert opinion: Preclinical studies demonstrated that PDGF inhibition with receptor antagonists such as imatinib reduces vascular remodeling. Therefore, PDGF might represent a plausible therapeutic target in this disease. However, compounds able to block this pathway via different mechanisms might also become potential PAH therapies.

Publication types

  • Review

MeSH terms

  • Animals
  • Familial Primary Pulmonary Hypertension
  • Humans
  • Hypertension, Pulmonary / drug therapy
  • Hypertension, Pulmonary / metabolism*
  • Hypertension, Pulmonary / physiopathology
  • Platelet-Derived Growth Factor / antagonists & inhibitors
  • Platelet-Derived Growth Factor / metabolism*
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Platelet-Derived Growth Factor
  • Protein Kinase Inhibitors