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Unloaded heart in vivo replicates fetal gene expression of cardiac hypertrophy

Nature Medicine volume 4, pages 1269–1275 (1998)Cite this article

Abstract

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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Figure 1: Expression of TGFβ1, TGFβ3 and c-fos transcripts.
Figure 2: Expression of MHC, GLUT and CPT I mRNA isoforms.
Figure 3: Western immunoanalysis of GLUT1 and GLUT4 proteins obtained from control (C) and transplanted hearts (T) excised 1 and 7 days (d) after transplantation.
Figure 4: Levels of GLUT4 (a) and muscle-specific CPT I (b) mRNA in controls, hearts unloaded for 48 hours, and unloaded hearts after reloading in a working heart apparatus for 60 min.
Figure 5

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Acknowledgements

We thank F.J. Clubb and P. Potts (Texas Heart Institute) for histological preparations, and V. Gaussin for critically reviewing the manuscript. This work was supported in part by grant RO1-HL43133 and NIH-RI-A139026 from the US Public Health Service. C.D. is the recipient of a Daland Fellowship from the American Philosophical Society.

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Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine University of Texas Houston Medical School, 6431 Fannin, Houston, 77030, Texas, USA

    Christophe Depre, Qiuying Han, Torsten Doenst, Meredith L. Moore & Heinrich Taegtmeyer

  2. Department of Integrative Biology and Pharmacology University of Texas Houston Medical School, University of Texas Houston Medical School, 6431 Fannin, Houston, 77030, Texas, USA

    Gregory L. Shipley & Peter J.A. Davies

  3. Division of Organ Transplantation, Department of Surgery University of Texas Houston Medical School, 6431 Fannin, Houston, 77030, Texas, USA

    Wenhao Chen & Stanislaw Stepkowski

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Correspondence to Heinrich Taegtmeyer.

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Depre, C., Shipley, G., Chen, W. et al. Unloaded heart in vivo replicates fetal gene expression of cardiac hypertrophy. Nat Med 4, 1269–1275 (1998). https://doi.org/10.1038/3253

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