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Titolo:
Ex vivo antisense oligonucleotides to proliferating cell nuclear antigen and Cdc2 kinase inhibit graft coronary artery disease
Autore:
Miniati, DN; Hoyt, EG; Feeley, BT; Poston, RS; Robbins, RC;
Indirizzi:
Stanford Univ, Sch Med, Dept Cardiothorac Surg, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 iothorac Surg, Stanford, CA 94305 USA
Titolo Testata:
CIRCULATION
fascicolo: 19, volume: 102, anno: 2000, supplemento:, S
pagine: 237 - 242
SICI:
0009-7322(20001107)102:19<237:EVAOTP>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-BETA; CARDIAC ALLOGRAFT VASCULOPATHY; NEOINTIMAL HYPERPLASIA; VEIN GRAFTS; EXPRESSION; OLIGODEOXYNUCLEOTIDES; TRANSPLANTATION; FACTOR-BETA(1); TRANSFECTION; PREVENTION;
Keywords:
transplantation; coronary disease; immunology; muscle, smooth; growth substances;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Robbins, RC Stanford Univ, Sch Med, Dept Cardiothorac Surg, Falk Cardiovasc Res Bldg, Stanford, CA 94305 USA Stanford Univ Falk Cardiovasc Res Bldg Stanford CA USA 94305 A
Citazione:
D.N. Miniati et al., "Ex vivo antisense oligonucleotides to proliferating cell nuclear antigen and Cdc2 kinase inhibit graft coronary artery disease", CIRCULATION, 102(19), 2000, pp. 237-242

Abstract

Background-The long-term success of cardiac transplantation is limited by graft coronary artery disease (GCAD). Antisense oligonucleotides (ASs) to proliferating cell nuclear antigen (PCNA) and Cdc2 kinase (Cdc2 k) can arrest cell cycle progression and inhibit neointimal hyperplasia. Transforming growth factor-beta (1) (TGF-beta (1)) has been implicated in vascular smoothmuscle cell (VSMC) activation. The role of TGF-beta (1) in GCAD remains unclear. We hypothesized that ASs to PCNA and Cdc2 k would inhibit VSMC proliferation and GCAD. Methods and Results-In vitro VSMC proliferation was determined after pretreatment with AS solution or medium alone followed by angiotensin II stimulation. PVG-to-ACI rat heterotopic cardiac transplantation procedures were performed after ex vivo pressure-mediated transfection of ASs to PCNA and Cdc2k or saline alone. At postoperative days 30, 60, and 90, allografts were assessed for GCAD, percent neointimal macrophages and VSMCs, and TGF-beta (1) activity. AS pretreatment significantly attenuated VSMC proliferation. Atpostoperative day 90, percent affected arteries, percent occlusion, and intima-media ratio demonstrated severe GCAD in saline-treated allografts, whereas these parameters were significantly lower in AS-treated allografts. Percent neointimal macrophages and VSMCs was reduced in AS-treated allografts, TGF-beta (1) activity was increased in saline compared with AS-treated allografts and nontransplanted heart controls. Conclusions-ASs to PCNA and Cdc2 k inhibit VSMC proliferation in vitro andreduce GCAD, percent neointimal VSMCs and macrophages, and TGF-beta1 activity in vivo. TGF-beta (1) may play a "response to injury" role in the development of GCAD. The prevention of GCAD via AS inhibition of cell cycle regulatory genes before reperfusion may offer a useful clinical alternative to current therapeutic strategies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 08:30:24