Transcriptional adaptation at the heart ta mechanical unloading

Novel strategies in the treatment of heart failure include mechanical unloa ding with a left ventricular assist device. Although first considered as a bridge to cardiac transplantation, this surgical treatment may improve card iac function in patients with heart failure, even after removal of the devi ce. The molecular adaptation of the heart to unloading remains largely unkn own. Most of the enzymes involved in the regulation of myocardial energetic s (including contractile proteins, ion pumps, and metabolic enzymes) exist in "fetal" and "adult" isoforms. It is known that cardiac hypertrophy due t o increased work load in vivo involves a switching from the normally expres sed adult isoform to the fetal isoform, Our work has now shown that the sam e pattern occurs in the unloaded heart. In both conditions, this switching is accompanied by the reexpression of growth factors and proto-oncogenes, T he functional improvement of the failing heart after mechanical unloading m ay in part be the result of a reexpression of fetal genes. (C)1999 by Excer pta Medico, Inc.