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Regulation of myocardial betaARK1 expression in catecholamine-induced cardiac hypertrophy in transgenic mice overexpressing alpha1B-adrenergic receptors.

Publication ,  Journal Article
Iaccarino, G; Keys, JR; Rapacciuolo, A; Shotwell, KF; Lefkowitz, RJ; Rockman, HA; Koch, WJ
Published in: J Am Coll Cardiol
August 2001

OBJECTIVES: Using a transgenic mouse model of myocardial-targeted overexpression of the wild-type alpha1B adrenergic receptor (AR) (Tg alpha43), we studied the role of the betaAR kinase (betaARK1) in the evolution of myocardial hypertrophy and its transition to heart failure (HF). BACKGROUND: Increased myocardial expression of betaARK1 has been shown to be associated with HF and certain models of hypertrophy. METHODS: Tg alpha43 mice and their nontransgenic littermate controls were treated with the alpha1AR agonist phenylephrine (PE) for 3, 7 or 14 days to characterize the cardiac consequences. RESULTS: Nontransgenic littermate control mice treated for 14 days with PE display cardiac hypertrophy with no increase in betaARK1 expression. However, Tg alpha43 animals show a reduced tolerance to 14-day PE treatment, demonstrated by reduced survival and severe cardiac hypertrophy. Moreover, PE treatment for three and seven days in Tg alpha43 mice resulted in an exaggerated hypertrophic response accompanied by significant cardiac biochemical abnormalities that are normally associated with HF, including fetal gene expression, reduced betaAR density and enhanced betaARK1 expression. We also found reduced myocardial stores of the sympathetic neurotransmitter neuropeptide Y. CONCLUSIONS: These data suggest that PE-treated Tg alpha43 mice have chronic activation of the cardiac sympathetic nervous system, which may be responsible for the appearance of apparent maladaptive hypertrophy with an evolution towards HF and sudden death. Thus, the cardiac phenotypes found in these mice are not the direct result of enhanced alpha1B AR signaling and suggest that betaARK1 is a key molecule in the transition of myocardial hypertrophy to HF.

Duke Scholars

Published In

J Am Coll Cardiol

DOI

ISSN

0735-1097

Publication Date

August 2001

Volume

38

Issue

2

Start / End Page

534 / 540

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, alpha-1
  • RNA, Messenger
  • Phenylephrine
  • Organ Size
  • Neuropeptide Y
  • Myocardium
  • Muscle Proteins
 

Citation

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Iaccarino, G., Keys, J. R., Rapacciuolo, A., Shotwell, K. F., Lefkowitz, R. J., Rockman, H. A., & Koch, W. J. (2001). Regulation of myocardial betaARK1 expression in catecholamine-induced cardiac hypertrophy in transgenic mice overexpressing alpha1B-adrenergic receptors. J Am Coll Cardiol, 38(2), 534–540. https://doi.org/10.1016/s0735-1097(01)01396-1
Iaccarino, G., J. R. Keys, A. Rapacciuolo, K. F. Shotwell, R. J. Lefkowitz, H. A. Rockman, and W. J. Koch. “Regulation of myocardial betaARK1 expression in catecholamine-induced cardiac hypertrophy in transgenic mice overexpressing alpha1B-adrenergic receptors.J Am Coll Cardiol 38, no. 2 (August 2001): 534–40. https://doi.org/10.1016/s0735-1097(01)01396-1.
Iaccarino G, Keys JR, Rapacciuolo A, Shotwell KF, Lefkowitz RJ, Rockman HA, et al. Regulation of myocardial betaARK1 expression in catecholamine-induced cardiac hypertrophy in transgenic mice overexpressing alpha1B-adrenergic receptors. J Am Coll Cardiol. 2001 Aug;38(2):534–40.
Iaccarino, G., et al. “Regulation of myocardial betaARK1 expression in catecholamine-induced cardiac hypertrophy in transgenic mice overexpressing alpha1B-adrenergic receptors.J Am Coll Cardiol, vol. 38, no. 2, Aug. 2001, pp. 534–40. Pubmed, doi:10.1016/s0735-1097(01)01396-1.
Iaccarino G, Keys JR, Rapacciuolo A, Shotwell KF, Lefkowitz RJ, Rockman HA, Koch WJ. Regulation of myocardial betaARK1 expression in catecholamine-induced cardiac hypertrophy in transgenic mice overexpressing alpha1B-adrenergic receptors. J Am Coll Cardiol. 2001 Aug;38(2):534–540.
Journal cover image

Published In

J Am Coll Cardiol

DOI

ISSN

0735-1097

Publication Date

August 2001

Volume

38

Issue

2

Start / End Page

534 / 540

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, alpha-1
  • RNA, Messenger
  • Phenylephrine
  • Organ Size
  • Neuropeptide Y
  • Myocardium
  • Muscle Proteins