Kawahira Y, Sawa Y, Nishimura M, Sakakida S, Ueda H, Kaneda Y, Matsuda H
First Department of Surgery, Osaka University Medical School, Japan.
Circulation. 1998 Nov 10;98(19 Suppl):II262-7; discussion II267-8.
In the failing heart, the density and affinity of beta-adrenergic receptors in the myocardium both tend to decrease as the severity of cardiac dysfunction increases. If this suppression of beta-adrenergic receptors could be prevented or reversed, this could serve as a fundamental form of treatment for the failing heart. We report here a possible new therapeutic approach for the failing heart involving the transfer of the beta 2-adrenergic receptor (B2AR) gene.
The B2AR cDNA was transfected in vivo to the concentric hypertrophied rat heart by intracoronary infusion with a hemagglutinating virus of Japan liposome method, and the transfected heart was transplanted into the abdomen of another rat. Four days after transfection, the sarcolemma of the cardiomyocytes was well labeled by immunohistochemical labeling. An overexpression of BAR of approximately 5 times in the heart (140 +/- 35 versus 24 +/- 3 fmol/mg protein for the transfected versus control hearts) was demonstrated by a ligand binding assay. The cardiac response of the transfected heart to isoproterenol was shown to be enhanced in a Langendorff perfusion system: After isoproterenol, developed pressure and maximal derivative of the left ventricle were greater than in the control heart (260 +/- 20 versus 230 +/- 10 mm Hg and 5500 +/- 300 versus 4500 +/- 300 mm Hg/s), and the minimal derivative of the left ventricle was remarkably smaller (-4500 +/- 300 versus -3300 +/- 200 mm Hg/s).
These results indicate that in vivo transfection of the gene for B2AR enhances the cardiac response to isoproterenol in the pressure-overloaded rat heart (in which the disease causes a decrease in receptor density), suggesting that transfer of this gene by intracoronary infusion during cardiac arrest has potential as a novel therapeutic approach for failing hearts.
