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Titolo:
Adenovirus-mediated lung vascular endothelial growth factor overexpressionprotects against hypoxic pulmonary hypertension in rats
Autore:
Partovian, C; Adnot, S; Raffestin, B; Louzier, V; Levame, M; Mavier, IM; Lemarchand, P; Eddahibi, S;
Indirizzi:
Hop Henri Mondor, Fac Med, Dept Physiol, INSERM,U492, F-94010 Creteil, France Hop Henri Mondor Creteil France F-94010 RM,U492, F-94010 Creteil, France Hop Henri Mondor, Serv Pharmacol Clin, F-94010 Creteil, France Hop Henri Mondor Creteil France F-94010 ol Clin, F-94010 Creteil, France Hop Ambroise Pare, Dept Physiol, Boulogne, France Hop Ambroise Pare Boulogne France Pare, Dept Physiol, Boulogne, France Hop Necker Enfants Malad, INSERM, U25, Paris, France Hop Necker Enfants Malad Paris France Malad, INSERM, U25, Paris, France
Titolo Testata:
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
fascicolo: 6, volume: 23, anno: 2000,
pagine: 762 - 771
SICI:
1044-1549(200012)23:6<762:ALVEGF>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTRAMUSCULAR GENE-TRANSFER; NITRIC-OXIDE; COLLATERAL DEVELOPMENT; EXPRESSION; SYNTHASE; TISSUE; ANGIOGENESIS; CIRCULATION; PHVEGF(165); ISCHEMIA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Adnot, S Hop Henri Mondor, Fac Med, Dept Physiol, INSERM,U492, 8 Rue Gen Sarrail, F-94010 Creteil, France Hop Henri Mondor 8 Rue Gen Sarrail CreteilFrance F-94010 France
Citazione:
C. Partovian et al., "Adenovirus-mediated lung vascular endothelial growth factor overexpressionprotects against hypoxic pulmonary hypertension in rats", AM J RESP C, 23(6), 2000, pp. 762-771

Abstract

Chronic hypoxic pulmonary hypertension (PH) is associated with vasoconstriction and structural remodeling of pulmonary vessels including narrowing ofthe arterial lumen and loss of distal functional arteries. To test whetherlung overexpression of the angiogenic factor vascular endothelial growth factor (VEGF) is beneficial in hypoxic PH, recombinant adenovirus encoding the human VEGF 165 gene under the control of a cytomegalovirus promoter (Ad.VEGF) or control vector containing no gene in the expression cassette (Ad.Null) was administered intratracheally to rats. With Ad.VEGF (10(8) plaque-forming units [pfu]), VEGF protein was present in bronchoalveolar ravage fluid as early as 2 d and until 17 d after gene transfer, but was not detectedin serum. Only small patchy areas of mononuclear cells without cell damage, edema, or hemorrhage were observed on lung histology with no significant change in lung permeability. In rats pretreated with Ad.VEGF (10(8) pfu) 2 d before a 2-wk exposure to hypoxia (10% O-2), lower values versus Ad.Null-pretreated controls were found for pulmonary artery pressure (25 +/- 1 versus 30 +/- 2 mm Hg, P < 0.05), right ventricular over left ventricular-plus-septum weight (0.37 +/- 0.01 versus 0.47 +/- 0.02, P < 0.001), normalized wall thickness of 50- to 200-mum vessels (P < 0.001), and muscularization ofdistal vessels (P < 0.001). Pretreatment with Ad.VEGF (108 pfu) increased endothelial nitric oxide synthase activity in lung tissue and partially restored endothelium-dependent vasodilation in isolated lungs from chronicallyhypoxic rats, as assessed by improvement of ionophore A23187-induced vasodilation and attenuation of endothelin-1 (300 pmol)-induced vasoconstriction, an effect abolished in the presence of nitro-1-arginine methylester. We conclude that adenoviral-mediated VEGF overexpression in the lungs attenuates development of hypoxic PH, in part by protecting endothelium-dependent function.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 03:22:31