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Titolo:
CELL-CYCLE INHIBITION PRESERVES ENDOTHELIAL FUNCTION IN GENETICALLY-ENGINEERED RABBIT VEIN GRAFTS
Autore:
MANN MJ; GIBBONS GH; TSAO PS; VONDERLEYEN HE; COOKE JP; BUITRAGO R; KERNOFF R; DZAU VJ;
Indirizzi:
HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV CARDIOVASC MED,THORN 12,75 FRANCIS ST BOSTON MA 02115 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV CARDIOVASC MED BOSTON MA 02115 STANFORD UNIV,SCH MED,DEPT SURG STANFORD CA 94305 STANFORD UNIV,SCH MED,FALK CARDIOVASC RES CTR,DIV CARDIOVASC MED STANFORD CA 94305
Titolo Testata:
The Journal of clinical investigation
fascicolo: 6, volume: 99, anno: 1997,
pagine: 1295 - 1301
SICI:
0021-9738(1997)99:6<1295:CIPEFI>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
SUPEROXIDE ANION PRODUCTION; HUMAN CORONARY-ARTERY; HUMAN SAPHENOUS-VEIN; BYPASS GRAFTS; DEPENDENT RELAXATION; SMOOTH-MUSCLE; INTIMAL HYPERPLASIA; L-ARGININE; EXPRESSION; ADHESION;
Keywords:
GENE THERAPY; CELL CYCLE; ENDOTHELIUM; CARDIOVASCULAR SURGERY; ANTISENSE OLIGONUCLEOTIDES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
38
Recensione:
Indirizzi per estratti:
Citazione:
M.J. Mann et al., "CELL-CYCLE INHIBITION PRESERVES ENDOTHELIAL FUNCTION IN GENETICALLY-ENGINEERED RABBIT VEIN GRAFTS", The Journal of clinical investigation, 99(6), 1997, pp. 1295-1301

Abstract

We have recently shown that ex vivo gene therapy of rabbit autologousvein grafts with antisense oligodeoxynucleotides (AS ODN) blocking cell cycle regulatory gene expression inhibits not only neointimal hyperplasia, but also diet-induced, accelerated graft atherosclerosis. We observed that these grafts remained free of macrophage invasion and foam cell deposition. Since endothelial dysfunction plays an important role in vascular disease, the current study examined the effect of this genetic engineering strategy on graft endothelial function and its potential relationship to the engineered vessels' resistance to atherosclerosis. Rabbit vein grafts transfected with AS ODN against proliferating cell nuclear antigen (PCNA) and cell division cycle 2 (cdc2) kinaseelaborated significantly more nitric oxide and exhibited greater vasorelaxation to both calcium ionophore and acetylcholine than did untreated or control ODN-treated grafts. This preservation of endothelial function was associated with a reduction in superoxide radical generation, vascular cell adhesion molecule-1 (VCAM-1) expression, and monocytebinding activity in grafts in both normal and hypercholesterolemic rabbits. Our data demonstrate that AS ODN arrest of vascular cell cycle progression results in the preservation of normal endothelial phenotype and function, thereby influencing the biology of the vessel wall towards a reduction of its susceptibility to occlusive disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 05:13:47