当前位置： SCI文献检索 > JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY期刊下所有文献 > Intracoronary Cytoprotective Gene Therapy: A Study of VEGF-B167 in a Pre-Clinical Animal Model of Dilated Cardiomyopathy.

Intracoronary Cytoprotective Gene Therapy: A Study of VEGF-B167 in a Pre-Clinical Animal Model of Dilated Cardiomyopathy.

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.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Woitek F,Zentilin L,Hoffman NE,Powers JC,Ottiger I,Parikh S,Kulczycki AM,Hurst M,Ring N,Wang T,Shaikh F,Gross P,Singh H,Kolpakov MA,Linke A,Houser SR,Rizzo V,Sabri A,Madesh M,Giacca M,Recchia FA

doi

10.1016/j.jacc.2015.04.071

subject

Has Abstract

pub_date

2015-07-14 00:00:00

pages

139-53

issue

2

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(15)02394-3

journal_volume

66

pub_type

杂志文章

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