Elevated Myocardial Akt Signaling Ameliorates Doxorubicin-induced Congestive Heart Failure and Promotes Heart Growth

Abstract 

Y. Taniyama and K. Walsh. Elevated Myocardial Akt Signaling Ameliorates Doxorubicin-induced Congestive Heart Failure and Promotes Heart Growth. Journal of Molecular and Cellular Cardiology (2002) 34, 1241–1247. Doxorubicin is a chemotherapeutic agent that can induce cardiotoxicity and congestive heart failure (CHF). In this study we tested whether intracoronary Akt1 gene delivery could inhibit doxorubicin-induced CHF. Saline or a replication defective adenoviral vector expressing constitutively-active Akt1 (myrAkt) or β-galactosidase (βgal) was delivered to the myocardium of 8 week old rats one day prior to initiating doxorubicin administration. In animals receiving saline or βgal, doxorubicin resulted in significant decreases in cardiac function and retarded post-natal heart growth at the 5 weeks time point. In contrast, transduction of myrAkt protected hearts against doxorubicin-induced decreases in fractional shortening and cardiac index, and improved left ventricular function at 5 weeks time point. Delivery of myrAkt also reversed the doxorubicin-induced reduction in post-natal heart growth and diminished lung edema. These data show that myocardial Akt can inhibit doxorubicin-induced reductions in cardiac function and growth, suggesting that manipulation of this signaling pathway may have utility for the treatment of congestive heart failure.

Keywords: Doxorubicin, Akt signaling, congestive heart failure, Adenovirus, Gene therapy

No full text is available. To read the body of this article, please view the PDF online.

• f1 Please address all correspondence to: Kenneth Walsh, PhD, Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA. Tel: 617-414-2392; Fax: 617-414-2391; E-mail:kxwalsh@bu.edu