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Titolo:
Intravascular adenovirus-mediated VEGF-C gene transfer reduces neointima formation in balloon-denuded rabbit aorta
Autore:
Hiltunen, MO; Laitinen, M; Turunen, MP; Jeltsch, M; Hartikainen, J; Rissanen, TT; Laukkanen, J; Niemi, M; Kossila, M; Hakkinen, TP; Kivela, A; Enholm, B; Mansukoski, H; Turunen, AM; Alitalo, K; Yla-Herttuala, S;
Indirizzi:
Univ Kuopio, AI Virtanen Inst, Dept Mol Med, FIN-70211 Kuopio, Finland Univ Kuopio Kuopio Finland FIN-70211 Mol Med, FIN-70211 Kuopio, Finland Univ Kuopio, AI Virtanen Inst, Dept Med, FIN-70211 Kuopio, Finland Univ Kuopio Kuopio Finland FIN-70211 Dept Med, FIN-70211 Kuopio, Finland Univ Kuopio, AI Virtanen Inst, Gene Therapy Unit, FIN-70211 Kuopio, Finland Univ Kuopio Kuopio Finland FIN-70211 apy Unit, FIN-70211 Kuopio, Finland Univ Helsinki, Haartman Inst, Mol Canc Biol Lab, Helsinki, Finland Univ Helsinki Helsinki Finland st, Mol Canc Biol Lab, Helsinki, Finland
Titolo Testata:
CIRCULATION
fascicolo: 18, volume: 102, anno: 2000,
pagine: 2262 - 2268
SICI:
0009-7322(20001031)102:18<2262:IAVGTR>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE CELLS; IN-VITRO; ANGIOGENESIS; HYPERPLASIA; EXPRESSION; INJECTION; ARTERIES;
Keywords:
viruses; genes; restenosis; growth substances;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Yla-Herttuala, S Univ Kuopio, AI Virtanen Inst, Dept Mol Med, POB 1627, FIN-70211 Kuopio, Finland Univ Kuopio POB 1627 Kuopio Finland FIN-70211 o, Finland
Citazione:
M.O. Hiltunen et al., "Intravascular adenovirus-mediated VEGF-C gene transfer reduces neointima formation in balloon-denuded rabbit aorta", CIRCULATION, 102(18), 2000, pp. 2262-2268

Abstract

Background-Gene transfer to the vessel wall may provide new possibilities for the treatment of vascular disorders, such as postangioplasty restenosis. In this study, we analyzed the effects of adenovirus-mediated vascular endothelial growth factor (VEGF)-C gene transfer on neointima formation afterendothelial denudation in rabbits. For comparison, a second group was treated with VEGF-A adenovirus and a third group with lacZ adenovirus. Clinical-grade adenoviruses were used for the study. Methods and Results-Aortas of cholesterol-fed New Zealand White rabbits were balloon-denuded, and gene transfer was performed 3 days later, Animals were euthanized 2 and 4 weeks after the gene transfer, and intima/media ratio (I/M), histology, and cell proliferation were analyzed. Two weeks after the gene transfer, I/M in the lacZ-transfected control group was 0.57+/-0.04. VEGF-C gene transfer reduced I/M to 0.38+/-0.02 (P<0.05 versus lacZ group). I/M in VEGF-A-treated animals was 0.49+/-0.17 (P=NS). The tendency that both VEGF groups had smaller I/M persisted at the 4-week time point, when the lac group had an I/M of 0.73+/-0.16, the VEGF-C group 0.44+/-0.14, and the VEGF-A group 0.63+/-0.21 (P=NS). Expression of VEGF receptors 1, 2, and 3 was detected in the vessel wall by immunocytochemistry and in situ hybridization. As an additional control, the effect of adenovirus on cell proliferation was analyzed by performing gene transfer to intact aorta without endothelial denudation. No differences were seen in smooth muscle cell proliferation or I/M between lacZ adenovirus and 0.9% saline-treated animals. Conclusions-Adenovirus-mediated VEGF-C gene transfer may be useful for thetreatment of postangioplasty restenosis and vessel wall thickening after vascular manipulations.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 08:50:01