Platelet-derived Endothelial Cell Growth Factor Gene Therapy for Arterial Intimal Thickening.

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TP/PD-ECGF has a chemotactic, but not a proliferative, effect on endothelial cells. Although TP/PD-ECGF has no mitogenic effect on endothelial cells, such as that of vascular endothelial growth factor. Taking these observations together with our previous in vivo study into account, we believe that TP/PD-ECGF has a strong angiogenic effect. However, the effect of TP/PD-ECGF on other types of vascular cells, especially VSMCs, required further consideration.2-French balloon catheters were inserted into the aorta of male rats through the right external carotid artery, and angioplasty of the right common carotid artery was performed by retracting the balloon catheter 3 times. A chitosan hydrogel containing pCIhTP/PD-ECGF or pCILacZ (pCI plasmid vector encoding TP/PD-ECGF gene or LacZ gene) was applied around the common carotid artery for gene delivery. Rats were killed 14 days later for measurement of neointima formation.X-gal staining revealed that chitosan hydrogel induced strong gene expression in the adventitia and vascular wall, and neointimal formation was significantly reduced in TP/PD-ECGF-treated rats 14 days after arterial injury. Immunohistochemical staining for smooth muscle cell arufa-actin demonstrated that neointima is composed predominantly of VSMCs in the pCI/LacZ treated groups, but there were fewer VSMCs in the pCIhTP group.These effects of TP/PDECGF indicate an ability to decrease neointimal smooth muscle cell proliferation and migration, which are therapeutically important because of their role in reducing neointimal mass in occlusive vascular diseases and inhibiting further neointimal growth.