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Evidence of dysfunction of endothelial progenitors in pulmonary arterial hypertension.

Abstract：

RATIONALE:Severe pulmonary arterial hypertension (PAH) is characterized by the formation of plexiform lesions and concentric intimal fibrosis in small pulmonary arteries. The origin of cells contributing to these vascular lesions is uncertain. Endogenous endothelial progenitor cells are potential contributors to this process. OBJECTIVES:To determine whether progenitors are involved in the pathobiology of PAH. METHODS:We performed immunohistochemistry to determine the expression of progenitor cell markers (CD133 and c-Kit) and the major homing signal pathway stromal cell-derived factor-1 and its chemokine receptor (CXCR4) in lung tissue from patients with idiopathic PAH, familial PAH, and PAH associated with congenital heart disease. Two separate flow cytometric methods were employed to determine peripheral blood circulating numbers of angiogenic progenitors. Late-outgrowth progenitor cells were expanded ex vivo from the peripheral blood of patients with mutations in the gene encoding bone morphogenetic protein receptor type II (BMPRII), and functional assays of migration, proliferation, and angiogenesis were undertaken. measurements and main results: There was a striking up-regulation of progenitor cell markers in remodeled arteries from all patients with PAH, specifically in plexiform lesions. These lesions also displayed increased stromal cell-derived factor-1 expression. Circulating angiogenic progenitor numbers in patients with PAH were increased compared with control subjects and functional studies of late-outgrowth progenitor cells from patients with PAH with BMPRII mutations revealed a hyperproliferative phenotype with impaired ability to form vascular networks. CONCLUSIONS:These findings provide evidence of the involvement of progenitor cells in the vascular remodeling associated with PAH. Dysfunction of circulating progenitors in PAH may contribute to this process.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Toshner M,Voswinckel R,Southwood M,Al-Lamki R,Howard LS,Marchesan D,Yang J,Suntharalingam J,Soon E,Exley A,Stewart S,Hecker M,Zhu Z,Gehling U,Seeger W,Pepke-Zaba J,Morrell NW

doi

10.1164/rccm.200810-1662OC

subject

Has Abstract

pub_date

2009-10-15 00:00:00

pages

780-7

issue

eissn

1073-449X

issn

1535-4970

pii

200810-1662OC

journal_volume

180

pub_type

杂志文章

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Evidence of dysfunction of endothelial progenitors in pulmonary arterial hypertension.