Journal of Cardiovascular Translational Research

, Volume 6, Issue 5, pp 852–860

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
Article

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.

Keywords

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

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Niels Thue Olsen
    • 1
    • 2
  • Veronica L. Dimaano
    • 1
  • Thomas Fritz-Hansen
    • 2
  • Peter Sogaard
    • 3
  • Khalid Chakir
    • 1
  • Kristian Eskesen
    • 1
    • 2
  • Charles Steenbergen
    • 1
  • David A. Kass
    • 1
  • Theodore P. Abraham
    • 1
  1. 1.Division of CardiologyJohns Hopkins Medical InstitutionsBaltimoreUSA
  2. 2.Department of CardiologyGentofte University HospitalCopenhagenDenmark
  3. 3.Faculty of Health SciencesAalborg UniversityAalborgDenmark

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