ArticleJournal of vascular surgery2014
In vivo electroporation of constitutively expressed HIF-1α plasmid DNA improves neovascularization in a mouse model of limb ischemia.
Article in Journal of vascular surgery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Arbitrary CaFrontiers in pharmacology · 2022Article
- Non-viral gene delivery of HIF-1α promotes angiogenesis in human adipose-derived stem cells.Acta biomaterialia · 2020Article
- Muscle Arnt/Hif1β Is Dispensable in Myofiber Type Determination, Vascularization and Insulin Sensitivity.PloS one · 2016Article
- Endogenously generated omega-3 fatty acids attenuate vascular inflammation and neointimal hyperplasia by interaction with free fatty acid receptor 4 in mice.Journal of the American Heart Association · 2015Article
- Optimizing in vivo gene transfer into mouse corpus cavernosum by use of surface electroporation.Korean journal of urology · 2015Article
- Therapeutic manipulation of angiogenesis with miR-27b.Vascular cell · 2015Article
- Sensitization of group III and IV muscle afferents in the mouse after ischemia and reperfusion injury.The journal of pain · 2014Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectiveHypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that stimulates angiogenesis during tissue ischemia. In vivo electroporation (EP) enhances tissue DNA transfection. We hypothesized that in vivo EP of plasmid DNA encoding a constitutively expressed HIF-1α gene enhances neovascularization compared with intramuscular (IM) injection alone.
methodsLeft femoral artery ligation was performed in mice assigned to three groups: (1) HIF-EP (n = 13); (2) HIF-IM (n = 14); and (3) empty plasmid (pVAX)-EP (n = 12). A single dose of HIF-1α or pVAX DNA (20 μL of 5 μg/μL each) was injected into the ischemic adductor muscle followed by EP (groups one and three). Mice in group two received IM injection of HIF-1α plasmid DNA alone. From preligation to days 0, 3, 7, 14, and 21 postligation, limb perfusion recovery quantified by laser Doppler perfusion imager, limb function, and limb necrosis were measured. On day 21, the surviving mice (4-5 per group) were sacrificed and adductor muscle tissues stained for necrosis using hematoxylin and eosin, capillary density (anti-CD31 antibodies), and collateral vessels via anti-α-smooth muscle actin antibodies.
resultsIn vivo EP of HIF-1α DNA significantly improved limb perfusion (HIF-EP: 1.03 ± 0.15 vs HIF-IM: 0.78 ± 0.064; P < .05, vs pVAX-EP: 0.41 ± 0.019; P < .001), limb functional recovery (HIF-EP: 3.5 ± 0.58 vs HIF-IM, 2.4 ± 1.14; P < .05, vs pVAX-EP: 2.4 ± 1.14; P < .001), and limb autoamputation on day 21 (HIF-EP: 77% ± 12% vs HIF-IM: 43% ± 14%; P < .05 vs pVAX-EP: 17% ± 11%; P < .01). Adductor muscle tissue necrosis decreased (HIF-EP: 20.7% ± 1.75% vs HIF-IM: 44% ± 3.73; P < .001, vs pVAX-EP: 60.05% ± 2.17%; P < .0001), capillary density increased (HIF-EP: 96.83 ± 5.72 vessels/high-powered field [hpf] vs HIF-IM: 62.87 ± 2.0 vessels/hpf; P < .001, vs pVAX-EP: 39.37 ± 2.76 vessels/hpf; P < .0001), collateral vessel formation increased (HI-EP: 76.33 ± 1.94 vessels/hpf vs HIF-IM: 37.5 ± 1.56 vessels/hpf; P < .0001, vs pVAX-EP: 18.5 ± 1.34 vessels/hpf; P < .00001), and the vessels were larger (HIF-EP: 15,521.67 ± 1298.16 μm(2) vs HIF-IM: 7788.87 ± 392.04 μm(2); P < .001 vs pVAX-EP: 4640.25 ± 614.01 μm(2); P < .0001).
conclusionsIn vivo EP-mediated delivery of HIF-1α plasmid DNA improves neovascularization in a mouse model of limb ischemia and is a potentially suitable nonviral, noninvasive intervention to facilitate therapeutic angiogenesis in critical limb ischemia.
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