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

被引：366

作者：

Perros, Frederic ^{[1
,2
,3
]}

Montani, David ^{[1
,2
]}

Dorfmueller, Peter ^{[1
,2
]}

Durand-Gasselin, Ingrid ^{[2
]}

Tcherakian, Colas ^{[1
,2
]}

Le Pavec, Jerome ^{[1
]}

Mazmanian, Michel ^{[3
]}

Fadel, Elie ^{[3
]}

Mussot, Sacha ^{[3
]}

Mercier, Olaf ^{[3
]}

Herve, Philippe ^{[3
]}

Emilie, Dominique ^{[2
]}

Eddahibi, Saadia ^{[4
]}

Simonneau, Gerald ^{[1
]}

Souza, Rogerio ^{[1
,2
]}

Humbert, Marc ^{[1
,2
]}

机构：

[1] Univ Paris 11, Serv Pneumol & Reanimat Resp,Hop Antoine Beclere, UPRES EA 2705,Inst Paris Sud Cytokines,Assistance, Ctr Natl Reference Hypertens Arterielle Pulm, F-92140 Clamart, France

[2] INSERM U764, Clamart, France

[3] Univ Paris 11, UPRES EA 2705, Chirurg Expt Lab, Ctr Chirurg Marie Lannelongue, Le Plessis Robinson, France

[4] Hop Henri Mondor, Assistance Publ Hop Paris, Dept Physiol Explorat Fonct, F-94010 Creteil, France

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2008年 / 178卷 / 01期

关键词：

imatinib; pulmonary arterial hypertension; platelet-derived growth factor; remodeling; smooth muscle cells;

D O I：

10.1164/rccm.200707-1037OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

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 tran scription-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 PA5MCs. 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 blotanalysis 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 PDCF-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.

引用

页码：81 / 88

页数：8

共 26 条

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