Regulation of myocardial βARK1 expression in catecholamine-induced cardiac hypertrophy in transgenic mice overexpressing α1B--adrenergic receptors

Guido Iaccarino, Janelle R. Keys, Antonio Rapacciuolo, Kyle F. Shotwell, Robert J. Lefkowitz, Howard A. Rockman, Walter J. Koch

Research output: Contribution to journalArticle


OBJECTIVES: Using a transgenic mouse model of myocardial-targeted overexpression of the wild-type α1B adrenergic receptor (AR) (Tgα43), we studied the role of the βAR kinase (βARK1) in the evolution of myocardial hypertrophy and its transition to heart failure (HF). BACKGROUND: Increased myocardial expression of βARK1 has been shown to be associated with HF and certain models of hypertrophy. METHODS: Tgα43 mice and their nontransgenic littermate controls were treated with the α1AR 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 βARK1 expression. However, Tgα43 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 Tgα43 mice resulted in an exaggerated hypertrophic response accompanied by significant cardiac biochemical abnormalities that are normally associated with HF, including fetal gene expression, reduced βAR density and enhanced βARK1 expression. We also found reduced myocardial stores of the sympathetic neurotransmitter neuropeptide Y. CONCLUSIONS: These data suggest that PE-treated Tgα43 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 α1BAR signaling and suggest that βARK1 is a key molecule in the transition of myocardial hypertrophy to HF.

Original languageEnglish
Pages (from-to)534-540
Number of pages7
JournalJournal of the American College of Cardiology
Issue number2
Publication statusPublished - 2001


ASJC Scopus subject areas

  • Nursing(all)

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