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The therapeutic effect of vascular endothelial growth factor gene- or heme oxygenase-1 gene-modified endothelial progenitor cells on neovascularization of rat hindlimb ischemia model.

Abstract：

OBJECTIVE:To explore the therapeutic potential of endothelial progenitor cells (EPCs) transfected with vascular endothelial growth factor A (VEGFA) and heme oxygenase-1 (HO-1) on rat hindlimb ischemia model. METHODS:Eukaryotic expression vectors encoding VEGFA or HO-1 were constructed and introduced into EPCs isolated from rat bone marrow. In total, 150 Sprague Dawley rat hindlimb ischemia models were established and randomized into five groups which were injected via tail vein with phosphate-buffered saline (PBS), nontransfected EPCs, VEGFA-modified EPCs, HO-1-modified EPCs, and both VEGFA- and HO-1-modified EPCs, respectively. The microvessel density, the expressions of VEGFA and HO-1 in the ischemic limbs, the recovery of blood flow as evaluated by laser-Doppler perfusion imaging, and the rate of limb salvage were compared among different groups. RESULTS:Transplantation of both VEGFA- and HO-1-modified EPCs in recipient rats significantly increased the microvessel density (expressed as capillaries/m(2) at day 21 after operation, group vascular endothelial growth factor (VEGF)+HO-1, 357 ± 14.1; group VEGF, 253.7 ± 9.9; group HO-1, 255.5 ± 12.5; group EPC, 210.7 ± 10.3; group PBS, 144.3 ± 9.3; P < .001), the expressions of VEGFA and HO-1 in ischemic tissue, the recovery of blood flow (at day 21, VEGF+HO-1 group, 85.4 ± 17.8%; VEGF group, 51.2 ± 13.2%; HO-1 group, 50.4 ± 12.9%; EPC group, 39.9 ± 8.5%; PBS group, 28.3 ± 7.8%; P < .001), and the rate of limb salvage (VEGF+HO-1 group, 94.4%; VEGF group or HO-1 group, 63.6%; EPC group, 50.0%; PBS group, 11.1%), compared with transplantation of either VEGFA- or HO-1-modified EPCs alone, or of nontransfected EPCs, or PBS injection. The order of therapeutic effectiveness on ischemic limbs was VEGFA- + HO-1-modifed EPC > either VEGFA- or HO-1-modified EPC alone > nontransfected EPC > PBS. CONCLUSIONS:VEGFA-modified EPC and HO-1-modified EPC synergized with each other in promoting angiogenesis in ischemic limbs of rat hindlimb ischemia model. In addition to VEGF, the introduction of HO-1 in EPC-based transplantation may serve as a novel and useful therapeutic strategy for ischemic disease of lower extremity.

journal_name

J Vasc Surg

journal_title

Journal of vascular surgery

authors

Long J,Wang S,Zhang Y,Liu X,Zhang H,Wang S

doi

10.1016/j.jvs.2012.11.096

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

756-65.e2

issue

eissn

0741-5214

issn

1097-6809

pii

S0741-5214(12)02677-8

journal_volume

pub_type

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The therapeutic effect of vascular endothelial growth factor gene- or heme oxygenase-1 gene-modified endothelial progenitor cells on neovascularization of rat hindlimb ischemia model.