Abstract 372: β1-adrenergic Receptor Blockade and Cardiac β2 Overexpression Stimulates Angiogenesis in the Failing Heart
β-adrenergic receptor (β-AR) antagonists play a favourable role on 3AR dysfunction in the failing heart (HF). Accordingly, β2-AR cardiac overexpression, through adenoviral gene delivery, improves β-AR signalling and myocardial contractility in post-infarcted hearts. The effects of improvement of 3AR function on angiogenesis mechanisms in HF have never been investigated. The aim of this study was to explore the cardiac pro-angiogenic properties of β1-AR selective blockade and adenoviral-mediated β2-AR overexpression in a rat model of post-ischemic HF. At 1 month post-surgical ligation of left anterior descending coronary artery, 80 adult 4-month-old male WKY rats with an infarct size 3 40% (assessed by Echo) were randomized into 4 groups: Group 1 (Controls), Group 2 (treated with Bisoprolol 1mg/Kg/die for 1 month), Group 3 (infected with adenoviral β2-AR intramyocardial gene delivery, 4x1011 pfu), Group 4 (infected with adeno-GFP). 10 sham-operated animals were also included. β2-AR overexpression was assessed at 6 days post-infection by immunohistochemistry. After 1 month, cardiac performance was evaluated in vivo by echocardiography and in vitro by single myocyte contractility, myocardial blood flow (MBF) and coronary flow reserve (CFR) by dyed beads dilution assay, cardiac capillary density by histology, cardiac β-AR signalling by β-AR density, GRK2 expression, and ISO-stimulated cAMP production, and, finally, cardiac VEGF expression by immunoblotting. Data are illustrated in the table⇓. Our results indicate that β1-AR blockade and cardiac β2-AR overexpression stimulate angiogenesis, increase myocardial perfusion, restore β-AR signalling, and improve failing myocyte contractility. The reduced cardiac VEGF levels reflect the comprehensive improvement in local ischemia induced by the 2 different therapeutical approaches.