A novel gene therapy for congestive heart failure.

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Beta adrenergic receptor system has a major important role in cardiac contraction. If the receptor can be increased by exogenous administration in the hearts in which the receptor is downregulated, this approach may improve the cardiac function. To test whether in-vivo gene transfection of beta 2 adrenergic receptor (B2AR) into the normal and the failing heart by constriction of the abdominal aorta can enhance cardiac function, we transfected with cDNA of the receptor in the heart of Sprague-Dawley rat by intracoronary infusion of hemaagglutinating virus of Japan (HVJ) -liposome plasmid complex including human B2AR gene (BAR (+) and pBAR (+) group). Control hearts were infused with HVJ-liposome plasmid complex without the receptor gene (BAR (-) and pBAR (-) group). Four days after transfection, the hearts were examined. Immunohistochemical labeling using specific antibody to human B2AR demonstrated that the sarcolemma of the myocytes in BAR (+) and pBAR (+) groups was well labeled, while anywhere in BAR (-) and pBAR (-) groups was not. Ligand binding assay using [125I] -cyanopindolol revealed that the receptor density of the hearts in BAR (+) and pBAR (+) groups was significantly higher than in BAR (-) and pBAR (-) groups. Evaluation using Langendorff system demonstrated that developed pressure and maximum derivative of the left ventricle after infusion of isoproterenol were significantly higher in BAR (+) and pBAR (+) groups than in BAR(-) and pBAR (-) groups. Minimum derivative of the left ventricle after infusion of isoproterenol was significantly lower in BAR (+) and pBAR (+) groups than in BAR (-) and pBAR (-) groups. Our results indicated that beta 2 adrenergic receptor was overexpressed approximately 4 times in normal rat hearts and the failing heart by pressure overload by in-vivo gene transfection using HVJ liposome method and the transfected hearts demonstrated marked enhancements in cardiac response after infusion of isoproterenol.