Platelet-derived endothelial cell growth factor gene therapy for limb ischemia

Abstract

This study demonstrated that PD-ECGF/TP gene transfer induced angiogenesis and decreased ischemia in a rabbit hindlimb model by promoting arteriogenesis, suggesting that targeting this gene may be a promising therapeutic strategy for peripheral vascular disease.

Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia

“…In effect, the follow-up duration of most pre-clinical studies reporting benefits of gene therapy strategies on hindlimb ischemia has ranged from 1 week to 30 days. [22][23][24][25][26][27] Beneficial effects at longer follow-up times (up to 12 weeks) of AdVEGF 121 have been reported by Gowdak et al 28 in rats and rabbits with hindlimb ischemia. However, their results are not strictly comparable with ours because the gene was injected between 2 and 4 weeks before the induction of hindlimb ischemia.…”

Adventitial delivery of platelet-derived endothelial cell growth factor gene prevented intimal hyperplasia of vein graft

“…12,13,33 In our previous study, we demonstrated the therapeutic effects of PD-ECGF/TP gene transfer on ischemia by promoting angiogenesis and inhibiting apoptosis (summary in Fig 5). [27][28][29] Sengupta et al 33 have reported that equimolar concentrations of PD-ECGF/TP induce a similar total monolayer recovery of wounded endothelium in vitro as well as vascular endothelial growth factor, strongly suggesting the chemotaxis functional effect of PD-ECGF/TP on endothelium. Therefore, as shown in Fig 5, we speculate that in addition to the suppressive effect of PD-ECGF/TP on VSMCs, PD-ECGF/TP itself, its enzymatic substrates, or PD-ECGF/TP-derived HO-1 expression may promote endothelial cell proliferation and protect endothelial cells from injury.…”

“…15,[27][28][29] We used gene transfection of human PD-ECGF/TP into rat VSMCs to study the mechanism of inhibitory effect of PD-ECGF/TP on VSMC, and found that inhibition of VSMC proliferation was correlated with the upregulation of p27 KIP1 and HO-1. 15 We also found that adventitial gene transfer of TP/PD-ECGF in a balloon injury rat carotid artery model markedly inhibited the intimal hyperplasia.…”

The Role of Angiogenic Growth Factors in Arteriogenesis

“…In some studies, intramuscular transfection was used to stimulate arteriogenesis [29,30,31]. However, although collateral artery growth can be enhanced, this method is not able to specifically target collateral arteries.…”