Intracoronary Cytoprotective Gene Therapy: A Study of VEGF-B167 in a Pre-Clinical Animal Model of Dilated Cardiomyopathy.
J Am Coll Cardiol
; 66(2): 139-53, 2015 Jul 14.
Article
en En
| MEDLINE
| ID: mdl-26160630
ABSTRACT
BACKGROUND:
Vascular endothelial growth factor (VEGF)-B activates cytoprotective/antiapoptotic and minimally angiogenic mechanisms via VEGF receptors. Therefore, VEGF-B might be an ideal candidate for the treatment of dilated cardiomyopathy, which displays modest microvascular rarefaction and increased rate of apoptosis.OBJECTIVES:
This study evaluated VEGF-B gene therapy in a canine model of tachypacing-induced dilated cardiomyopathy.METHODS:
Chronically instrumented dogs underwent cardiac tachypacing for 28 days. Adeno-associated virus serotype 9 viral vectors carrying VEGF-B167 genes were infused intracoronarily at the beginning of the pacing protocol or during compensated heart failure. Moreover, we tested a novel VEGF-B167 transgene controlled by the atrial natriuretic factor promoter.RESULTS:
Compared with control subjects, VEGF-B167 markedly preserved diastolic and contractile function and attenuated ventricular chamber remodeling, halting the progression from compensated to decompensated heart failure. Atrial natriuretic factor-VEGF-B167 expression was low in normally functioning hearts and stimulated by cardiac pacing; it thus functioned as an ideal therapeutic transgene, active only under pathological conditions.CONCLUSIONS:
Our results, obtained with a standard technique of interventional cardiology in a clinically relevant animal model, support VEGF-B167 gene transfer as an affordable and effective new therapy for nonischemic heart failure.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Cardiomiopatía Dilatada
/
Terapia Genética
/
Factor B de Crecimiento Endotelial Vascular
Tipo de estudio:
Guideline
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Am Coll Cardiol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Alemania