Platelet-derived growth factor expression and function in idiopathic pulmonary arterial hypertension

Am J Respir Crit Care Med. 2008 Jul 1;178(1):81-8. doi: 10.1164/rccm.200707-1037OC. Epub 2008 Apr 17.


Rationale: Platelet-derived growth factor (PDGF) promotes the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), and may play a role in the progression of pulmonary arterial hypertension (PAH), a condition characterized by proliferation of PASMCs resulting in the obstruction of small pulmonary arteries.

Objectives: To analyze the expression and pathogenic role of PDGF in idiopathic PAH.

Methods: PDGF and PDGF receptor mRNA expression was studied by real-time reverse transcription-polymerase chain reaction performed on laser capture microdissected pulmonary arteries from patients undergoing lung transplantation for idiopathic PAH. Immunohistochemistry was used to localize PDGF, PDGF receptors, and phosphorylated PDGFR-beta. The effects of imatinib on PDGF-B-induced proliferation and chemotaxis were tested on human PASMCs.

Measurements and main results: PDGF-A, PDGF-B, PDGFR-alpha, and PDGFR-beta mRNA expression was increased in small pulmonary arteries from patients displaying idiopathic PAH, as compared with control subjects. Western blot analysis revealed a significant increase in protein expression of PDGFR-beta in PAH lungs, as compared with control lungs. In small remodeled pulmonary arteries, PDGF-A and PDGF-B mainly localized to PASMCs and endothelial cells (perivascular inflammatory infiltrates, when present, showed intensive staining), PDGFR-alpha and PDGFR-beta mainly stained PASMCs and to a lesser extent endothelial cells. Proliferating pulmonary vascular lesions stained phosphorylated PDGFR-beta. PDGF-BB-induced proliferation and migration of PASMCs were inhibited by imatinib. This effect was not due to PASMC apoptosis.

Conclusions: PDGF may play an important role in human PAH. Novel therapeutic strategies targeting the PDGF pathway should be tested in clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Becaplermin
  • Benzamides
  • Cell Count
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Humans
  • Hypertension, Pulmonary / metabolism*
  • Hypertension, Pulmonary / pathology
  • Imatinib Mesylate
  • Lung / metabolism
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Phosphorylation
  • Piperazines / pharmacology
  • Platelet-Derived Growth Factor / metabolism*
  • Platelet-Derived Growth Factor / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-sis
  • Pulmonary Artery / metabolism*
  • Pulmonary Artery / pathology
  • Pyrimidines / pharmacology
  • RNA, Messenger / metabolism
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Receptors, Platelet-Derived Growth Factor / metabolism


  • Benzamides
  • Piperazines
  • Platelet-Derived Growth Factor
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-sis
  • Pyrimidines
  • RNA, Messenger
  • Becaplermin
  • Imatinib Mesylate
  • Receptor, Platelet-Derived Growth Factor beta
  • Receptors, Platelet-Derived Growth Factor