Modulation of graft arteriosclerosis in a rat carotid transplantation model.
J Surg Res
; 145(1): 161-9, 2008 Mar.
Article
en En
| MEDLINE
| ID: mdl-18164034
BACKGROUND: Venous autografts used in cardiovascular surgery tend to deteriorate over time due to arteriosclerotic complications. Cadaveric vascular allografts represent a possible alternative for this application, but donor endothelial cells (ECs) and antigen presenting cells of the graft trigger alloresponses mediated by MHC class I (MHC I) antigen, leading to graft failure. Vascular allograft rejection might be prevented by reducing cell surface expression of MHC I and thereby lowering the immunogenicity of the grafts. MATERIAL AND METHODS: An Intrabody approach was used to reduce MHC I expression in vascular allografts. The efficacy of an adenovirus (Ad) carrying an anti-MHC I Intrabody gene (Ad-Intrabody) was first tested in vitro using rat aortic ECs. The effect of the Ad-Intrabody was then studied in vivo by a model of rat carotid artery transplantation. Grafts were analyzed 7 and 28 days after transplantation by immunohistochemistry and real time reverse transcriptase-polymerase chain reaction. RESULTS: Ad-Intrabody gene transfer reduced MHC I surface expression of rat ECs and inhibited in vivo alloimmune responses to carotid allografts. Decreased T cell and macrophage infiltration was observed within Ad-Intrabody transduced arterial allografts at day 28. This was associated with an inhibition of intimal thickening formation. Analysis of mRNA showed diminished levels of T cell markers and Interferon-gamma expression in the Ad-Intrabody-treated group compared with control groups. CONCLUSIONS: Ex vivo adenoviral gene transfer of an Intrabody against MHC I into rat carotid arteries prior to transplantation reduced both graft arteriosclerosis and inflammation in the absence of any systemic immunosuppression.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arteriosclerosis
/
Inmunología del Trasplante
/
Antígenos de Histocompatibilidad Clase I
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Arterias Carótidas
/
Anticuerpos
Límite:
Animals
Idioma:
En
Revista:
J Surg Res
Año:
2008
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Estados Unidos