Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Focal angiogen therapy using intramyocardial delivery of an adenovirus vector coding for vascular endothelial growth factor 121
Autore:
Lee, LY; Patel, SR; Hackett, NR; Mack, CA; Polce, DR; El-Sawy, T; Hachamovitch, R; Zanzonico, P; Sanborn, TA; Parikh, M; Isom, OW; Crystal, RG; Rosengart, TK;
Indirizzi:
Cornell Univ, Med Ctr, New York Hosp,Div Nucl Med, Dept Cardiothorac Surg,Div Pulm & Crit Care Med, New York, NY 10021 USA Cornell Univ New York NY USA 10021 Crit Care Med, New York, NY 10021 USA Cornell Univ, Med Ctr, New York Hosp,, Div Cardiol, New York, NY 10021 USACornell Univ New York NY USA 10021 ,, Div Cardiol, New York, NY 10021 USA
Titolo Testata:
ANNALS OF THORACIC SURGERY
fascicolo: 1, volume: 69, anno: 2000,
pagine: 14 - 23
SICI:
0003-4975(200001)69:1<14:FATUID>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEDIATED GENE-TRANSFER; REPLICATION-DEFICIENT; MYOCARDIAL PERFUSION; FACTOR FAMILY; EXPRESSION; DISEASE; HEART; CELLS; FLOW;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Rosengart, TK Evanston Northwestern Healthcare, 2650 Ridge Ave, Evanston, IL 60201 USA Evanston Northwestern Healthcare 2650 Ridge Ave Evanston IL USA 60201
Citazione:
L.Y. Lee et al., "Focal angiogen therapy using intramyocardial delivery of an adenovirus vector coding for vascular endothelial growth factor 121", ANN THORAC, 69(1), 2000, pp. 14-23

Abstract

Background. Adenovirus (Ad) vector-mediated gene therapy strategies have emerged as promising modalities for the "biological revascularization" of tissues. We hypothesized that direct intramyocardial, as opposed to intracoronary, administration of an Ad vector coding for the vascular endothelial growth factor 121 cDNA (Ad(GV)VEGF121.10) would provide highly focal Ad genome levels, and increases in VEGF, ideal for inducing localized therapeutic angiogenesis. Methods. Persistence and regional distribution of the vector were assessedby TaqMan real-time quantitative polymerase chain reaction technology and enzyme-linked immunosorbent assay, after intramyocardial Ad(GV)VEGF121.10 in the rat, and either intramyocardial or intracoronary (circumflex territory) vector in Yorkshire swine. Based on these results, we assessed the focalnature of the improved cardiac blood flow in a previously reported porcinemyocardial ischemia model. Results. Intramyocardial delivery of Ad(GV)VEGF121.10 in the rat resulted in local persistence of the Ad genome that decreased 1,000-fold over 3 weeks, with peak myo-cardial VEGF expression 24 to 72 h after vector delivery. After intramyocardial Ad(GV)VEGF121.10 in the circumflex distribution of pigs, Ad vector genome and VEGF protein levels were more than 1,000-fold and more than 90-fold higher, respectively, in this distribution than in other myocardial regions. In comparison, intracoronary injection yielded maximum myocardial Ad genome and VEGF levels 33-fold and 9-fold lower, respectively, than that after intramyocardial delivery. Angiograms obtained 28 days after intramyocardial Ad(GV)VEGF121.10 demonstrated rapid circumflex reconstitution via collaterals localized to the region of vector administration. Conclusions. These studies demonstrate that direct intramyocardial administration of Ad(VG)VEGF121.10 results in focal genome and VEGF levels, including focal angiogenesis, sufficient to normalize blood flow to the ischemic myocardium, findings that are relevant to designing human trials of gene therapy-mediated cardiac angio genesis. (C) 2000 by The Society of Thoracic Surgeons.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/10/20 alle ore 00:39:10