Platelet-derived growth factor receptor-β and epidermal growth factor receptor in pulmonary vasculature of systemic sclerosis-associated pulmonary arterial hypertension versus idiopathic pulmonary arterial hypertension and pulmonReportar como inadecuado




Platelet-derived growth factor receptor-β and epidermal growth factor receptor in pulmonary vasculature of systemic sclerosis-associated pulmonary arterial hypertension versus idiopathic pulmonary arterial hypertension and pulmon - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Arthritis Research and Therapy

, 13:R61

First Online: 14 April 2011Received: 28 November 2009Revised: 19 February 2011Accepted: 14 April 2011

Abstract

IntroductionSystemic sclerosis SSc complicated by pulmonary arterial hypertension PAH carries a poor prognosis, despite pulmonary vascular dilating therapy. Platelet-derived growth factor receptor-β PDGFR-β and epidermal growth factor receptor EGFR are potential therapeutic targets for PAH because of their proliferative effects on vessel remodelling. To explore their role in SScPAH, we compared PDGFR- and EGFR-mmunoreactivity in lung tissue specimens from SScPAH. We compared staining patterns with idiopathic PAH IPAH and pulmonary veno-occlusive disease PVOD, as SScPAH vasculopathy differs from IPAH and sometimes displays features of PVOD. Immunoreactivity patterns of phosphorylated PDGFR-β pPDGFR-β and the ligand PDGF-B were evaluated to provide more insight into the patterns of PDGFR-b activation.

MethodsLung tissue specimens from five SScPAH, nine IPAH, six PVOD patients and five controls were examined. Immunoreactivity was scored for presence, distribution and intensity.

ResultsAll SScPAH and three of nine IPAH cases P = 0.03 showed PDGFR-β-immunoreactivity in small vessels arterioles-venules; of five SScPAH vs. two of nine IPAH cases P = 0.02 showed venous immunoreactivity. In small vessels, intensity was stronger in SScPAH vs. IPAH. No differences were found between SScPAH and PVOD. One of five normal controls demonstrated focally mild immunoreactivity. There were no differences in PDGF-ligand and pPDGFR-b-immunoreactivity between patient groups; however, pPDGFR-b-immunoreactivity tended to be more prevalent in SScPAH small vasculature compared to IPAH. Vascular EGFR-immunoreactivity was limited to arterial and arteriolar walls, without differences between groups. No immunoreactivity was observed in vasculature of normals.

ConclusionsPDGFR-β-immunoreactivity in SScPAH is more common and intense in small- and post-capillary vessels than in IPAH and does not differ from PVOD, fitting in with histomorphological distribution of vasculopathy. PDGFR-β immunoreactivity pattern is not paralleled by pPDGFR-β or PDGF-B patterns. PDGFR-β- and EGFR-immunoreactivity of pulmonary vessels distinguishes PAH patients from controls.

AbbreviationsEGFRepidermal growth factor receptor

IPAHidiopathic pulmonary arterial hypertension

PAHpulmonary arterial hypertension

PDGFR-βplateled-derived growth factor receptor-β

p PDGFR-βphosphorylated plateled-derived growth factor receptor-β

PVODpulmonary veno-occlusive disease

SScPAHsystemic sclerosis-associated pulmonary arterial hypertension.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3315 contains supplementary material, which is available to authorized users.

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Autor: Maria J Overbeek - Anco Boonstra - Alexandre E Voskuyl - Madelon C Vonk - Anton Vonk-Noordegraaf - Maria PA van Berkel -

Fuente: https://link.springer.com/







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