Unloaded heart in vivo replicates fetal gene expression of cardiac hypertrophy

Christophe Depre; Gregory L. Shipley; Wenhao Chen; Qiuying Han; Torsten Doenst; Meredith L. Moore; Stanislaw Stepkowski; Peter J.A. Davies; Heinrich Taegtmeyer

doi:10.1038/3253

Unloaded heart in vivo replicates fetal gene expression of cardiac hypertrophy

Christophe Depre, Gregory L. Shipley, Wenhao Chen, Qiuying Han, Torsten Doenst, Meredith L. Moore, Stanislaw Stepkowski, Peter J.A. Davies, Heinrich Taegtmeyer

Research output: Contribution to journal › Article › peer-review

370 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1269-1275
Number of pages	7
Journal	Nature Medicine
Volume	4
Issue number	11
DOIs	https://doi.org/10.1038/3253
State	Published - Nov 1998

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

Access to Document

10.1038/3253

Cite this

@article{88bd4f32e5544326ba30b93e35da33e7,

title = "Unloaded heart in vivo replicates fetal gene expression of cardiac hypertrophy",

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.",

author = "Christophe Depre and Shipley, {Gregory L.} and Wenhao Chen and Qiuying Han and Torsten Doenst and Moore, {Meredith L.} and Stanislaw Stepkowski and Davies, {Peter J.A.} and Heinrich Taegtmeyer",

note = "Funding Information: Acknowledgments 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.",

year = "1998",

month = nov,

doi = "10.1038/3253",

language = "English (US)",

volume = "4",

pages = "1269--1275",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

number = "11",

}

TY - JOUR

T1 - Unloaded heart in vivo replicates fetal gene expression of cardiac hypertrophy

AU - Depre, Christophe

AU - Shipley, Gregory L.

AU - Chen, Wenhao

AU - Han, Qiuying

AU - Doenst, Torsten

AU - Moore, Meredith L.

AU - Stepkowski, Stanislaw

AU - Davies, Peter J.A.

AU - Taegtmeyer, Heinrich

N1 - Funding Information: Acknowledgments 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.

PY - 1998/11

Y1 - 1998/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0031761451&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031761451&partnerID=8YFLogxK

U2 - 10.1038/3253

DO - 10.1038/3253

M3 - Article

C2 - 9809550

AN - SCOPUS:0031761451

SN - 1078-8956

VL - 4

SP - 1269

EP - 1275

JO - Nature Medicine

JF - Nature Medicine

IS - 11

ER -

Unloaded heart in vivo replicates fetal gene expression of cardiac hypertrophy

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this