In vivo transfer of human hepatocyte growth factor gene accelerates re-endothelialization and inhibits neointimal formation after balloon injury in rat model

Abstract

Although most therapeutic strategies to prevent restenosis are designed to inhibit vascular smooth muscle cell (VSMC) proliferation directly, VSMC proliferation might be indirectly inhibited by re-endothelialization, as endothelial cells secrete antiproliferative and antithrombotic substances. We hypothesized that application of an endothelium-specific growth factor to balloon-injured arteries could accelerate re-endothelialization, thereby attenuating intimal hyperplasia. In this study, we investigated in vivo gene transfer of human HGF that exclusively stimulated endothelial cells without replication of VSMC growth into injured vessels. Transfection of human HGF gene into rat balloon-injured carotid artery resulted in significant inhibition of neointimal formation up to at least 8 weeks after transfection, accompanied by detection of human immunoreactive HGF. Induction of re-endothelialization induced by overexpression of human HGF gene transfer into balloon-injured vessels is supported by

Molecular strategy using cis-element ‘decoy’ of E2F binding site inhibits neointimal formation in porcine balloon-injured coronary artery model

“…Since recent studies demonstrated the therapeutic efficacy of re-endothelialization using endothelium-specific growth factors, such as VEGF (vascular endothelial growth factor) or HGF (hepatocyte growth factor), 12,13 it is noteworthy to examine the effects of E2F decoy ODN on endothelial function. Thus, we measured the vasomotor response to an endothelium-dependent agonist.…”

Inhibition of Neointima by Angiotensin-Converting Enzyme Inhibitor in Porcine Coronary Artery Balloon-Injury Model

“…Indeed, overexpression of human HGF vector in rat ballooninjured vessels resulted in a significant increase in reendothelialized area as assessed by Evans' blue dye staining. 20 If so, enhanced reendothelialization by increased vascular HGF would result in restoration of anatomical integrity and recovery of physiological function. Therefore, we examined vasomotor response to an endothelium-dependent agonist.…”

Effect of nifedipine on endothelial function in normotensive smokers: potential contribution of increase in circulating hepatocyte growth factor

“…25 Moreover, our previous report demonstrated that the area covered by endothelial cells in rat balloon-injured vessels was significantly increased by in vivo transfer of the HGF gene. 26 We also demonstrated that Effect of nifedipine on endothelial function in smokers K Yamasaki et al administration of cilostazol improved endotheliumdependent vascular relaxation through induction of serum HGF in rat balloon-injured vessels. 27 These data, including the present findings, are consistent with our previous in vitro findings that the downregulation of HGF is caused by downregulated c-AMP and/or upregulated TGF-b in a hypoxic or high glucose condition which promotes atherosclerosis, and addition of HGF could rescue endothelial cells from death.…”