Neovascularization of ischemic tissues by gene delivery of the extracellular matrix protein Del-1
J. Clin. Invest. Jingping Zhong, et al. 112:30 doi:10.1172/JCI17034 [
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Figure 2Del-1 induces angiogenesis in rabbit model of ischemia. (
a) Angiography was performed after unilateral hind-limb ischemia induced in New Zealand white rabbits (3–4 kg body weight) by surgical resection of the femoral artery (
19). X’s indicate the ten sites in and surrounding the medial thigh (midthigh) (bracket) in the upper leg, where plasmid was injected (0.5 mg/site). (
b) Sustained transgene expression induced by plasmid injection in muscle was detected 1 month after therapy by RT-PCR for hVEGF
165 and hDel-1. VEGF or Del-1 gene expression was detected in
VEGF- or
Del-1–plasmid–injected muscle, respectively, but not in control plasmid–injected muscle. MW, molecular weight standards. (
c) Angiography was performed before and 1 month after therapy for each treatment. Brackets indicate medial thigh region. (
d) Mean number of new vessels (± SD) crossing the medial thigh (area under the brackets in
c) for each treatment 1 month after therapy. Asterisks indicate statistically significant result (
P < 0.01). (
e) Mean CD31 protein expression (± SD) in muscle tissue 1 month after therapy. CD31 levels within injected muscle were assessed by Western blot analysis of lysates of muscle tissue. Asterisks indicate statistically significant result relative to noncoding plasmid control (
P < 0.01). Statistical significance for angiography and CD31 analyses was assessed by one-way ANOVA with plasmid treatment as the main effect.