Nature Medicine
4, 1269 - 1275 (1998)
doi:10.1038/3253
Unloaded heart in vivo replicates fetal gene expression of cardiac
hypertrophyChristophe Depre1, Gregory L. Shipley2, Wenhao Chen3, Qiuying Han1, Torsten Doenst1, Meredith L. Moore1, Stanislaw Stepkowski3, Peter J.A. Davies2
& Heinrich Taegtmeyer11
Division of Cardiology, Department of Internal Medicine,
University of Texas Houston Medical School, 6431 Fannin,
Houston, Texas 77030, USA. 2
Department of Integrative Biology and Pharmacology,
University of Texas Houston Medical School, 6431 Fannin,
Houston, Texas 77030, USA. 3
Division of Organ Transplantation, Department of Surgery,
University of Texas Houston Medical School, 6431 Fannin,
Houston, Texas 77030, USA.
Correspondence should be addressed to Heinrich Taegtmeyer ht@heart.med.uth.tmc.edu
The cardiac response to increased work includes a reactivation of fetal
genes. The response to a decrease in cardiac work is not known. Such information
is of clinical interest, because mechanical unloading can improve the functional
capacity of the failing heart. We compared here the patterns of gene expression
in unloaded rat heart with those in hypertrophied rat heart. Both conditions
induced a re-expression of growth factors and proto-oncogenes, and a downregulation
of the 'adult' isoforms, but not of the 'fetal' isoforms, of proteins regulating
myocardial energetics. Therefore, opposite changes in cardiac workload
in vivo induce similar patterns of gene response. Reactivation of fetal
genes may underlie the functional improvement of an unloaded failing heart.
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