Abstract
Hepatic growth factor (HGF) has been widely used in studies on arterial remodeling after injury, and results turn out to be inconsistent. The changes of endogenous HGF expression after injury also remain controversial. This study clarified the role of exogenous human HGF (hHGF) gene transfer in neointimal hyperplasia and investigated the associated alterations of endogenous HGF and c-Met expressions under endothelial denudation with or without hHGF gene transfer using a balloon-injured rabbit aorta model. Sixty-one rabbits were randomly divided into normal controls, endothelial injury, endothelial injury with hHGF, or the control vector gene transfer groups. On weeks 1, 2, 4, and 8 after injury, neointimal hyperplasia and endothelialization were evaluated by the ratio of neointimal area to medial area (N/M ratio), CD31-positive staining, α-smooth muscle actin, and endothelial nitric oxide synthase expressions using histological analysis, immunohistochemistry staining, or real-time quantitative reverse transcriptase polymerase chain reaction. Endogenous rabbit HGF (rHGF) and c-Met expressions were detected with immunohistochemistry staining and quantitative reverse transcriptase polymerase chain reaction. It was found that expressions of endogeneous rHGF and c-Met in endothelial injury upregulated with peak levels on week 2 or week 4 after injury (p < 0.01). On week 1 after hHGF transfer, neointimal hyperplasia was significantly inhibited (p < 0.001), with decreased α-smooth muscle actin expression (p < 0.05) and improved endothelial cells regeneration and function (p < 0.01). More remarkable overexpression of endogenous rHGF and c-Met mRNAs were detected, and lowered positive staining of rHGF and c-Met was shown in the neointima (p < 0.05). These results demonstrated hHGF gene transfer induced further overexpression of endogenous rHGF and c-Met mRNAs but lowered immunoreactivities of rHGF and c-Met in the neointima, thus leading to significant attenuation of neointimal hyperplasia.
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