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

Autores
Olea, Fernanda Daniela; Vera Janavel, G.; Cuniberti, Luis Alberto; Yannarelli, Gustavo Gabriel; Cabeza Meckert, Patricia; Cors, J.; Valdivieso, L.; Lev, G.; Mendiz, O.; Bercovich, A.; Criscuolo, M.; Melo, C.; Laguens, R.; Crottogini, Alberto José
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Vascular endothelial growth factor (VEGF) gene transfer-mediated angiogenesis has been proposed for peripheral artery disease. However, protocols using single administration have shown little benefit. Given that the transient nature of VEGF gene expression provokes instability of neovasculature, we hypothesized that repeated administration would provide efficient tissue protection. We thus compared single vs repeated transfection in a rabbit model of hindlimb ischemia by injecting a plasmid encoding human VEGF165 (pVEGF165) at 7 (GI, n=10) or 7 and 21 (GII, n=10) days after surgery. Placebo animals (GIII, n=10) received empty plasmid. Fifty days after surgery, single and repeated administration similarly increased saphenous peak flow velocity and quantity of angiographically visible collaterals. However, microvasculature increased only with repeated transfection: capillary density was 49.4±15.4 capillaries per 100 myocytes in GI, 84.6±14.7 in GII (P<0.01 vs GI and GIII) and 49.3±13.6 in GIII, and arteriolar density was 1.9±0.6 arterioles per mm2 in GI, 3.0±0.9 in GII (P<0.01 vs GI and GIII) and 1.5±0.6 in GIII. Muscle lesions were reduced only within repeated transfection. With single administration, gene expression peaked at 7 days and declined rapidly, but with repeated administration, it remained positive at 50 days. At 90 days of repeated transfection (additional animals), gene expression decreased significantly, but neovessel densities did not. Thus, repeated, but not single, VEGF gene transfection resulted in increased microvasculature, which, in turn, afforded effective protection against ischemic muscle damage.
Fil: Olea, Fernanda Daniela. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Vera Janavel, G.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Cuniberti, Luis Alberto. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Yannarelli, Gustavo Gabriel. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cabeza Meckert, Patricia. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina
Fil: Cors, J.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Valdivieso, L.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Lev, G.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Mendiz, O.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Bercovich, A.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Criscuolo, M.. Biosidus S. A.; Argentina
Fil: Melo, C.. Biosidus S. A.; Argentina
Fil: Laguens, R.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Crottogini, Alberto José. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
VEGF
PERIPHERAL ARTERY DISEASE
ANGIOGENESIS
HINDLIMB ISCHEMIA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/96244
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/96244
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemiaOlea, Fernanda DanielaVera Janavel, G.Cuniberti, Luis AlbertoYannarelli, Gustavo GabrielCabeza Meckert, PatriciaCors, J.Valdivieso, L.Lev, G.Mendiz, O.Bercovich, A.Criscuolo, M.Melo, C.Laguens, R.Crottogini, Alberto JoséVEGFPERIPHERAL ARTERY DISEASEANGIOGENESISHINDLIMB ISCHEMIAhttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3Vascular endothelial growth factor (VEGF) gene transfer-mediated angiogenesis has been proposed for peripheral artery disease. However, protocols using single administration have shown little benefit. Given that the transient nature of VEGF gene expression provokes instability of neovasculature, we hypothesized that repeated administration would provide efficient tissue protection. We thus compared single vs repeated transfection in a rabbit model of hindlimb ischemia by injecting a plasmid encoding human VEGF165 (pVEGF165) at 7 (GI, n=10) or 7 and 21 (GII, n=10) days after surgery. Placebo animals (GIII, n=10) received empty plasmid. Fifty days after surgery, single and repeated administration similarly increased saphenous peak flow velocity and quantity of angiographically visible collaterals. However, microvasculature increased only with repeated transfection: capillary density was 49.4±15.4 capillaries per 100 myocytes in GI, 84.6±14.7 in GII (P<0.01 vs GI and GIII) and 49.3±13.6 in GIII, and arteriolar density was 1.9±0.6 arterioles per mm2 in GI, 3.0±0.9 in GII (P<0.01 vs GI and GIII) and 1.5±0.6 in GIII. Muscle lesions were reduced only within repeated transfection. With single administration, gene expression peaked at 7 days and declined rapidly, but with repeated administration, it remained positive at 50 days. At 90 days of repeated transfection (additional animals), gene expression decreased significantly, but neovessel densities did not. Thus, repeated, but not single, VEGF gene transfection resulted in increased microvasculature, which, in turn, afforded effective protection against ischemic muscle damage.Fil: Olea, Fernanda Daniela. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vera Janavel, G.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Cuniberti, Luis Alberto. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Yannarelli, Gustavo Gabriel. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabeza Meckert, Patricia. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Cors, J.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Valdivieso, L.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Lev, G.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Mendiz, O.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Bercovich, A.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Criscuolo, M.. Biosidus S. A.; ArgentinaFil: Melo, C.. Biosidus S. A.; ArgentinaFil: Laguens, R.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Crottogini, Alberto José. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaNature Publishing Group2009-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/96244Olea, Fernanda Daniela; Vera Janavel, G.; Cuniberti, Luis Alberto; Yannarelli, Gustavo Gabriel; Cabeza Meckert, Patricia; et al.; Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia; Nature Publishing Group; Gene Therapy; 16; 6; 6-2009; 716-7230969-7128CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/gt200930info:eu-repo/semantics/altIdentifier/doi/10.1038/gt.2009.30info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:40:51Zoai:ri.conicet.gov.ar:11336/96244instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:40:51.51CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia
title Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia
spellingShingle Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia
Olea, Fernanda Daniela
VEGF
PERIPHERAL ARTERY DISEASE
ANGIOGENESIS
HINDLIMB ISCHEMIA
title_short Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia
title_full Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia
title_fullStr Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia
title_full_unstemmed Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia
title_sort Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia
dc.creator.none.fl_str_mv Olea, Fernanda Daniela
Vera Janavel, G.
Cuniberti, Luis Alberto
Yannarelli, Gustavo Gabriel
Cabeza Meckert, Patricia
Cors, J.
Valdivieso, L.
Lev, G.
Mendiz, O.
Bercovich, A.
Criscuolo, M.
Melo, C.
Laguens, R.
Crottogini, Alberto José
author Olea, Fernanda Daniela
author_facet Olea, Fernanda Daniela
Vera Janavel, G.
Cuniberti, Luis Alberto
Yannarelli, Gustavo Gabriel
Cabeza Meckert, Patricia
Cors, J.
Valdivieso, L.
Lev, G.
Mendiz, O.
Bercovich, A.
Criscuolo, M.
Melo, C.
Laguens, R.
Crottogini, Alberto José
author_role author
author2 Vera Janavel, G.
Cuniberti, Luis Alberto
Yannarelli, Gustavo Gabriel
Cabeza Meckert, Patricia
Cors, J.
Valdivieso, L.
Lev, G.
Mendiz, O.
Bercovich, A.
Criscuolo, M.
Melo, C.
Laguens, R.
Crottogini, Alberto José
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv VEGF
PERIPHERAL ARTERY DISEASE
ANGIOGENESIS
HINDLIMB ISCHEMIA
topic VEGF
PERIPHERAL ARTERY DISEASE
ANGIOGENESIS
HINDLIMB ISCHEMIA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Vascular endothelial growth factor (VEGF) gene transfer-mediated angiogenesis has been proposed for peripheral artery disease. However, protocols using single administration have shown little benefit. Given that the transient nature of VEGF gene expression provokes instability of neovasculature, we hypothesized that repeated administration would provide efficient tissue protection. We thus compared single vs repeated transfection in a rabbit model of hindlimb ischemia by injecting a plasmid encoding human VEGF165 (pVEGF165) at 7 (GI, n=10) or 7 and 21 (GII, n=10) days after surgery. Placebo animals (GIII, n=10) received empty plasmid. Fifty days after surgery, single and repeated administration similarly increased saphenous peak flow velocity and quantity of angiographically visible collaterals. However, microvasculature increased only with repeated transfection: capillary density was 49.4±15.4 capillaries per 100 myocytes in GI, 84.6±14.7 in GII (P<0.01 vs GI and GIII) and 49.3±13.6 in GIII, and arteriolar density was 1.9±0.6 arterioles per mm2 in GI, 3.0±0.9 in GII (P<0.01 vs GI and GIII) and 1.5±0.6 in GIII. Muscle lesions were reduced only within repeated transfection. With single administration, gene expression peaked at 7 days and declined rapidly, but with repeated administration, it remained positive at 50 days. At 90 days of repeated transfection (additional animals), gene expression decreased significantly, but neovessel densities did not. Thus, repeated, but not single, VEGF gene transfection resulted in increased microvasculature, which, in turn, afforded effective protection against ischemic muscle damage.
Fil: Olea, Fernanda Daniela. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Vera Janavel, G.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Cuniberti, Luis Alberto. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Yannarelli, Gustavo Gabriel. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cabeza Meckert, Patricia. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina
Fil: Cors, J.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Valdivieso, L.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Lev, G.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Mendiz, O.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Bercovich, A.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Criscuolo, M.. Biosidus S. A.; Argentina
Fil: Melo, C.. Biosidus S. A.; Argentina
Fil: Laguens, R.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Crottogini, Alberto José. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Vascular endothelial growth factor (VEGF) gene transfer-mediated angiogenesis has been proposed for peripheral artery disease. However, protocols using single administration have shown little benefit. Given that the transient nature of VEGF gene expression provokes instability of neovasculature, we hypothesized that repeated administration would provide efficient tissue protection. We thus compared single vs repeated transfection in a rabbit model of hindlimb ischemia by injecting a plasmid encoding human VEGF165 (pVEGF165) at 7 (GI, n=10) or 7 and 21 (GII, n=10) days after surgery. Placebo animals (GIII, n=10) received empty plasmid. Fifty days after surgery, single and repeated administration similarly increased saphenous peak flow velocity and quantity of angiographically visible collaterals. However, microvasculature increased only with repeated transfection: capillary density was 49.4±15.4 capillaries per 100 myocytes in GI, 84.6±14.7 in GII (P<0.01 vs GI and GIII) and 49.3±13.6 in GIII, and arteriolar density was 1.9±0.6 arterioles per mm2 in GI, 3.0±0.9 in GII (P<0.01 vs GI and GIII) and 1.5±0.6 in GIII. Muscle lesions were reduced only within repeated transfection. With single administration, gene expression peaked at 7 days and declined rapidly, but with repeated administration, it remained positive at 50 days. At 90 days of repeated transfection (additional animals), gene expression decreased significantly, but neovessel densities did not. Thus, repeated, but not single, VEGF gene transfection resulted in increased microvasculature, which, in turn, afforded effective protection against ischemic muscle damage.
publishDate 2009
dc.date.none.fl_str_mv 2009-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/96244
Olea, Fernanda Daniela; Vera Janavel, G.; Cuniberti, Luis Alberto; Yannarelli, Gustavo Gabriel; Cabeza Meckert, Patricia; et al.; Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia; Nature Publishing Group; Gene Therapy; 16; 6; 6-2009; 716-723
0969-7128
CONICET Digital
CONICET
url http://hdl.handle.net/11336/96244
identifier_str_mv Olea, Fernanda Daniela; Vera Janavel, G.; Cuniberti, Luis Alberto; Yannarelli, Gustavo Gabriel; Cabeza Meckert, Patricia; et al.; Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia; Nature Publishing Group; Gene Therapy; 16; 6; 6-2009; 716-723
0969-7128
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/gt200930
info:eu-repo/semantics/altIdentifier/doi/10.1038/gt.2009.30
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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