Common Genomic Response in Different Mouse Models of β -Adrenergic-Induced Cardiomyopathy

Vinciane Gaussin, James E. Tomlinson, Christophe Depre, Stefan Engelhardt, Christopher L. Antos, Gen Takagi, Lutz Hein, James N. Topper, Stephen B. Liggett, Eric N. Olson, Martin J. Lohse, Stephen F. Vatner, Dorothy E. Vatner

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Background-Although β-adrenergic receptor (AR) blockade therapy is beneficial in the treatment of heart failure, little is known regarding the transcriptional mechanisms underlying this salutary action. Methods and Results-In the present study, we screened mice overexpressing Gsα, β1AR, β2AR, or protein kinase A to test if a common genomic pathway exists in different models with enhanced β-adrenergic signaling. In mice overexpressing Gsα, differentially expressed genes were identified by mRNA profiling. In addition to well-known markers of cardiac hypertrophy (atrial natriuretic factor, CARP, and β-myosin heavy chain), uncoupling protein 2 (UCP2), a protein involved in the control of mitochondrial membrane potential, and four-and-a-half LIM domain protein-1 (FHL1), a member of the LIM protein family, were predicted to be upregulated. Upregulation of these genes was confirmed by quantitative reverse transcriptase-polymerase chain reaction at all time points tested during the development of cardiomyopathy in mice overexpressing Gsα. In mice overexpressing β1AR, β2AR, or protein kinase A, increased UCP2 and FHL1 expression was also observed at the onset of cardiomyopathy. βAR blockade treatment reversed the cardiomyopathy and suppressed the increased expression of UCP2 and FHL1 in mice overexpressing Gsα. Conclusions-UCP2 and FHL1 are important candidate genes that correlate with the development of βAR-induced cardiomyopathy in different mouse models with enhanced βAR signaling. In addition to preserving cardiac function, βAR blockade treatment also prevents the genomic regulation that correlates with the onset of heart failure.

Original languageEnglish (US)
Pages (from-to)2926-2933
Number of pages8
JournalCirculation
Volume108
Issue number23
DOIs
StatePublished - Dec 9 2003

Fingerprint

Cardiomyopathies
Adrenergic Agents
Adrenergic Receptors
Cyclic AMP-Dependent Protein Kinases
LIM Domain Proteins
Heart Failure
Genes
Myosin Heavy Chains
Mitochondrial Membrane Potential
Cardiomegaly
Atrial Natriuretic Factor
Reverse Transcriptase Polymerase Chain Reaction
Treatment Failure
Proteins
Up-Regulation
Messenger RNA
Uncoupling Protein 2

Keywords

  • Cardiomyopathy
  • Genomics
  • Receptors, adrenergic, beta

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Gaussin, V., Tomlinson, J. E., Depre, C., Engelhardt, S., Antos, C. L., Takagi, G., ... Vatner, D. E. (2003). Common Genomic Response in Different Mouse Models of β -Adrenergic-Induced Cardiomyopathy. Circulation, 108(23), 2926-2933. https://doi.org/10.1161/01.CIR.0000101922.18151.7B

Common Genomic Response in Different Mouse Models of β -Adrenergic-Induced Cardiomyopathy. / Gaussin, Vinciane; Tomlinson, James E.; Depre, Christophe; Engelhardt, Stefan; Antos, Christopher L.; Takagi, Gen; Hein, Lutz; Topper, James N.; Liggett, Stephen B.; Olson, Eric N.; Lohse, Martin J.; Vatner, Stephen F.; Vatner, Dorothy E.

In: Circulation, Vol. 108, No. 23, 09.12.2003, p. 2926-2933.

Research output: Contribution to journalArticle

Gaussin, V, Tomlinson, JE, Depre, C, Engelhardt, S, Antos, CL, Takagi, G, Hein, L, Topper, JN, Liggett, SB, Olson, EN, Lohse, MJ, Vatner, SF & Vatner, DE 2003, 'Common Genomic Response in Different Mouse Models of β -Adrenergic-Induced Cardiomyopathy', Circulation, vol. 108, no. 23, pp. 2926-2933. https://doi.org/10.1161/01.CIR.0000101922.18151.7B
Gaussin V, Tomlinson JE, Depre C, Engelhardt S, Antos CL, Takagi G et al. Common Genomic Response in Different Mouse Models of β -Adrenergic-Induced Cardiomyopathy. Circulation. 2003 Dec 9;108(23):2926-2933. https://doi.org/10.1161/01.CIR.0000101922.18151.7B
Gaussin, Vinciane ; Tomlinson, James E. ; Depre, Christophe ; Engelhardt, Stefan ; Antos, Christopher L. ; Takagi, Gen ; Hein, Lutz ; Topper, James N. ; Liggett, Stephen B. ; Olson, Eric N. ; Lohse, Martin J. ; Vatner, Stephen F. ; Vatner, Dorothy E. / Common Genomic Response in Different Mouse Models of β -Adrenergic-Induced Cardiomyopathy. In: Circulation. 2003 ; Vol. 108, No. 23. pp. 2926-2933.
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AU - Antos, Christopher L.

AU - Takagi, Gen

AU - Hein, Lutz

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AU - Olson, Eric N.

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AU - Vatner, Stephen F.

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