Hypertrophy signaling pathways in experimental chronic aortic regurgitation

Niels Thue Olsen, Veronica L. Dimaano, Thomas Fritz-Hansen, Peter Sogaard, Khalid Chakir, Kristian Eskesen, Charles Steenbergen, David A. Kass, Theodore P. Abraham

Research output: Contribution to journalArticle

Abstract

The development of left ventricular hypertrophy and dysfunction in aortic regurgitation (AR) has only been sparsely studied experimentally. In a new model of chronic AR in rats, we examined activation of molecular pathways involved in myocardial hypertrophy. Chronic AR was produced by damaging one or two valve cusps, resulting in eccentric remodeling and left ventricular dysfunction, with no increase in overall fibrosis. Western blotting showed increased activation of Akt and p38 at 12 weeks and of c-Jun amino-terminal kinase at 2 weeks, decreased activation of extracellular regulated kinase 5 at both 2 and 12 weeks, while activation of calcium/calmodulin-dependent protein kinase II and extracellular regulated kinase 1/2 was unchanged. Expression of calcineurin and ANF was also unchanged. Eccentric hypertrophy and early cardiac dysfunction in experimental AR are associated with a pattern of activation of intracellular pathways different from that seen with pathological hypertrophy in pressure overload, and more similar to that associated with benign physiological hypertrophy.

Original languageEnglish (US)
Pages (from-to)852-860
Number of pages9
JournalJournal of Cardiovascular Translational Research
Volume6
Issue number5
DOIs
StatePublished - Oct 1 2013

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Keywords

  • Animal models of human disease remodeling
  • Aortic valve regurgitation
  • Hypertrophy
  • Proteins
  • Ventricular function

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

Olsen, N. T., Dimaano, V. L., Fritz-Hansen, T., Sogaard, P., Chakir, K., Eskesen, K., Steenbergen, C., Kass, D. A., & Abraham, T. P. (2013). Hypertrophy signaling pathways in experimental chronic aortic regurgitation. Journal of Cardiovascular Translational Research, 6(5), 852-860. https://doi.org/10.1007/s12265-013-9503-y