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

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

Author information

1
Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Service de Pneumologie et Réanimation Respiratoire, Institut Paris-Sud Cytokines, Hôpital Antoine-Béclère, Université Paris-Sud 11, UPRES EA 2705, Clamart, France.

Abstract

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.

PMID:
18420966
DOI:
10.1164/rccm.200707-1037OC
[Indexed for MEDLINE]

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