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Titolo:
Adenoviral-mediated expression of antisense RNA to basic fibroblast growthfactor reduces tangential stress in arterialized vein grafts
Autore:
Hanna, AK; Duran, WN; Leconte, I; Fox, JC; Neschis, DG; Hobson, RW; Golden, MA;
Indirizzi:
Yale Univ, Sch Med, Vasc Surg Sect, New Haven, CT 06520 USA Yale Univ NewHaven CT USA 06520 Vasc Surg Sect, New Haven, CT 06520 USA Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Div Vasc Surg, Newark, NJ 07103 USA Univ Med & Dent New Jersey Newark NJ USA 07103 Surg, Newark, NJ 07103 USA Univ Penn, Sch Med, Dept Surg, Div Vasc Surg, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Vasc Surg, Philadelphia, PA 19104 USA Univ Penn, Sch Med, Dept Med, Div Cardiol, Philadelphia, PA 19104 USA UnivPenn Philadelphia PA USA 19104 v Cardiol, Philadelphia, PA 19104 USA Wistar Inst, Philadelphia, PA 19104 USA Wistar Inst Philadelphia PA USA 19104 ar Inst, Philadelphia, PA 19104 USA
Titolo Testata:
JOURNAL OF VASCULAR SURGERY
fascicolo: 4, volume: 31, anno: 2000,
pagine: 770 - 780
SICI:
0741-5214(200004)31:4<770:AEOART>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
SMOOTH-MUSCLE CELLS; GENE-TRANSFER; INJURY; PROLIFERATION; HYPERPLASIA; VECTORS; FATE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
18
Recensione:
Indirizzi per estratti:
Indirizzo: Hanna, AK Yale Univ, Sch Med, Vasc Surg Sect, 333 Cedar St,FMB 137,POB 208062, New Haven, CT 06520 USA Yale Univ 333 Cedar St,FMB 137,POB 208062 New Haven CT USA 06520
Citazione:
A.K. Hanna et al., "Adenoviral-mediated expression of antisense RNA to basic fibroblast growthfactor reduces tangential stress in arterialized vein grafts", J VASC SURG, 31(4), 2000, pp. 770-780

Abstract

Purpose: The purpose of this study was to test whether basic fibroblast growth factor (bFGF) participates in arterialized vein graft remodeling. Methods: Rabbits underwent in vivo gene transfer and carotid interpositionvein grafting. Segments of external jugular vein were infected with an adenovirus that expressed antisense bFGF RNA (Ad.ASbFGF) at 1 x 10(10) PFU/mL to inhibit new synthesis of bFGF by cells in the vein graft wall. Control rabbits were: treated with either adenovirus that encoded beta-galactosidase(Ad.lacZ) at 1 x 10(10) PFU/mL or vehicle (phosphate-buffered saline solution [PBS]). At 3 days, 3 grafts per treatment group were harvested for the determination of gene expression of ASbFGF RNA by reverse transcriptase-polymerase chain reaction. Rabbits were killed, and perfusion was fixed 2 months after the grafting. Total wall thickness and lumen circumference of veingrafts and normal arteries were measured in cross sections. Calculated mean tangential stress (+/-SD) for the ASbFGF-treated group and controls was compared for significance. Grafts were immunohistochemically stained to assess bFGF protein production. Results: Only the grafts infected with the Ad.ASbFGF gene expressed ASbFGFRNA. Grafts that were treated with Ad.ASbFGF displayed lower tangential stress (10.9 +/- 2.3 dynes/cm(2)) than PBS alone (22 +/- 2.8 dynes/cm(2)) or Ad.lacZ-treated controls (20.6 +/- 5.4 dynes/cm(2); P < .001). Tangential stress in the Ad.ASbFGF group was comparable to a normal carotid artery (13.9 +/- 2.1 dynes/cm(2)). The difference in mean total wall thickness was significant among the 3 treatment groups: Ad.ASbFGF, 164 +/- 3.4 mu m); Ad.lacZ, 100 +/- 3.3 mu m; and PBS, 96 +/- 3.6 mu m; P < .01). Luminal circumference was not different among the groups. The Ad.ASbFGF-treated vein graft wall was composed of thick lavers of concentric smooth muscle cells and elastin fibers in contrast to the sponge-like appearance observed in control arterialized vein grafts. Reduction in bFGF protein was noted only in the Ad.ASbFGF-treated group. Conclusion: Inhibition of bFGF synthesis in vivo with the use of adenoviral gene transfer of antisense RNA to bFGF promotes a vein graft with decreased tangential stress while maintaining the luminal area. The vein graft mall is remodeled and qualitatively resembles an artery so that wall tangential stress in Ad.ASbFGF and normal artery are not significantly different. The lack of significant difference in lumen circumference among groups suggests that wall thickening in the Ad.ASbFGF grafts is not at the expense of luminal narrowing. Our results suggest that ASbFGF RNA expression may represent an effective strategy in limiting the failure of arterialized venous conduits.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/10/20 alle ore 12:20:49