Intracoronary Cytoprotective Gene Therapy

摘要: 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 increased rate apoptosis. Objectives This study evaluated gene therapy in a canine model tachypacing-induced cardiomyopathy. Methods Chronically instrumented dogs underwent cardiac tachypacing 28 days. Adeno-associated virus serotype 9 viral vectors carrying VEGF-B167 genes were infused intracoronarily at beginning pacing protocol or during compensated heart failure. Moreover, we tested novel transgene controlled by atrial natriuretic promoter. Results Compared with control subjects, markedly preserved diastolic contractile function attenuated ventricular chamber remodeling, halting progression from to decompensated Atrial factor–VEGF-B167 expression was low normally functioning hearts stimulated pacing; it thus functioned as therapeutic transgene, active only under pathological conditions. Conclusions Our results, obtained standard technique interventional cardiology clinically relevant animal model, support transfer affordable effective new nonischemic