Artículo
Effect of intramuscular baculovirus encoding mutant hypoxia-inducible factor 1-alpha on neovasculogenesis and ischemic muscle protection in rabbits with peripheral arterial disease
Giménez, Carlos Sebastián
; Castillo Velasquez, Martha Giovanna
; Simonin, Jorge Alejandro
; Nuñez Pedrozo, Cristian Nahuel
; Pascuali, Natalia Marisa
; Bauza, Maria del Rosario
; Locatelli, Paola
; López, Ayelén Emilce
; Belaich, Mariano Nicolas
; Mendiz, Alfredo O.; Crottogini, Alberto José
; Cuniberti, Luis Alberto
; Olea, Fernanda Daniela
Fecha de publicación:
10/2020
Editorial:
Taylor & Francis As
Revista:
Cytotherapy
ISSN:
1465-3249
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Background aims: Peripheral arterial disease (PAD) is a progressive, disabling ailment for which no effective treatment exists. Gene therapy-mediated neovascularization has emerged as a potentially useful strategy. We tested the angiogenic and arteriogenic efficacy and safety of a baculovirus (BV) encoding mutant, oxygen-resistant hypoxia-inducible factor 1-alpha (mHIF-1α), in rabbits with PAD. Methods: After assessing the transfection efficiency of the BV.mHIF-1α vector and its tubulogenesis potential in vitro, we randomized rabbits with experimental PAD to receive 1 × 109 copies of BV.mHIF-1α or BV.null (n = 6 per group) 7 days after surgery. Two weeks post-treatment, collateralization (digital angiography) and capillary and arteriolar densities (immunohistochemistry) were measured in the posterior limbs. Ischemic damage was evaluated in adductor and gastrocnemius muscle samples. Tracking of viral DNA in injected zones and remote tissues at different time points was performed in additional rabbits using a BV encoding GFP. Results: Angiographically visible collaterals were more numerous in BV.mHIF-1α-treated rabbits (8.12 ± 0.42 vs 6.13 ± 1.15 collaterals/cm2, P < 0.05). The same occurred with arteriolar (27.9 ± 7.0 vs 15.3 ± 4.0 arterioles/mm2) and capillary (341.8 ± 109.9 vs 208.8 ± 87.7 capillaries/mm2, P < 0.05) densities. BV.mHIF-1α-treated rabbits displayed less ischemic muscle damage than BV.null-treated animals. Viral DNA and GFP mRNA were detectable only at 3 and 7 days after injection in hind limbs. Neither the virus nor GFP mRNA was detected in remote tissues. Conclusions: In rabbits with PAD, BV.mHIF-1α induced neovascularization and reduced ischemic damage, exhibiting a good safety profile at 14 days post-treatment. Complementary studies to evaluate its potential usefulness in the clinic are needed.
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Articulos (IMETTYB)
Articulos de INSTITUTO DE MEDICINA TRASLACIONAL, TRASPLANTE Y BIOINGENIERIA
Articulos de INSTITUTO DE MEDICINA TRASLACIONAL, TRASPLANTE Y BIOINGENIERIA
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Citación
Giménez, Carlos Sebastián; Castillo Velasquez, Martha Giovanna; Simonin, Jorge Alejandro; Nuñez Pedrozo, Cristian Nahuel; Pascuali, Natalia Marisa; et al.; Effect of intramuscular baculovirus encoding mutant hypoxia-inducible factor 1-alpha on neovasculogenesis and ischemic muscle protection in rabbits with peripheral arterial disease; Taylor & Francis As; Cytotherapy; 22; 10; 10-2020; 563-572
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