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Transfection of human hepatocyte growth factor gene inhibits advancing pulmonary arterial hypertension induced by shunt flow in a rabbit model.

Abstract：

:We investigated gene transfer with human hepatocyte growth factor (HGF) to suppress pulmonary arterial hypertension (PAH) produced by an arteriovenous shunt in a rabbit model. The rabbit model of advanced PAH was used to show that HGF targets pulmonary arteriolar endothelial cells and inhibits disease progression. In the PAH rabbit model transfected with the HGF gene, hemodynamic abnormalities and right ventricular hypertrophy were prevented, as confirmed by invasive measurements and electrocardiographic examinations. In addition to augmented expression of HGF, an increased number of pulmonary arterioles were detected by immunohistochemical analysis. Western Blot and real-time reverse transcriptase-polymerase chain reaction indicated increased protein and mRNA levels of HGF and endothelial nitricoxide synthase (eNOS) in lungs after HGF transfection. Notably, exogenous HGF reduced lung expression of endothelin-1 (ET-1), which was critically involved in PAH-related pathologic changes. Our results suggested that HGF transfection suppresses PAH induced by shunt flow through enhanced expression of HGF with subsequent regulation of the concentrations of eNOS and ET-1 secreted by endothelial cells thereby promoting angiogenesis in injured lung tissue.

journal_name

Transplant Proc

journal_title

Transplantation proceedings

authors

Liu R,Wu S,Cao G,Wang W,Liu K,Wu S

doi

10.1016/j.transproceed.2012.07.158

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

705-12

issue

2

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(12)01345-0

journal_volume

45

pub_type

杂志文章

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