The Journal of Thoracic and Cardiovascular Surgery
Volume 133, Issue 1 , Pages 37-43, January 2007

Roles of cyclooxygenase-2 and phosphorylated Akt (Thr308) in cardiac hypertrophy regression mediated by left-ventricular unloading

  • Jeremias Wohlschlaeger, MD

      Affiliations

    • Department of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Germany
    • J. W. and K. J. S. contributed equally to the study.
    • ,
  • Klaus Jürgen Schmitz, MD

      Affiliations

    • Department of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Germany
    • J. W. and K. J. S. contributed equally to the study.
    • ,
  • Jenci Palatty

      Affiliations

    • Department of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Germany
    • ,
  • Atsushi Takeda, MD

      Affiliations

    • Faculty of Health Science, School of Physical Therapy, Gumma Paz College, Gumma, Japan
    • ,
  • Nobuakira Takeda, MD

      Affiliations

    • Department of Internal Medicine, Jikei University, Tokyo, Japan
    • ,
  • Christian Vahlhaus, MD

      Affiliations

    • Department of Cardiology and Angiology, University Hospital Münster, Germany
    • ,
  • Bodo Levkau, MD

      Affiliations

    • Division of Pathophysiology, Department of Internal Medicine, University Hospital Essen, University of Duisburg-Essen, Germany
    • ,
  • Jörg Stypmann, MD

      Affiliations

    • Department of Cardiology and Angiology, University Hospital Münster, Germany
    • ,
  • Christof Schmid, MD

      Affiliations

    • Department of Thoracic and Cardiovascular Surgery, University Hospital Münster, Germany.
    • ,
  • Kurt Werner Schmid, MD

      Affiliations

    • Department of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Germany
    • ,
  • Hideo Andreas Baba, MD

      Affiliations

    • Department of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Germany
    • Corresponding Author InformationReprint requests: Hideo Andreas Baba, MD, Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany

Received 10 May 2006; received in revised form 29 June 2006; accepted 31 July 2006.

Objectives

Cyclooxygenase-2 is associated with cardiac hypertrophy during chronic heart failure and is regulated through the PI3K/Akt pathway. Cyclooxygenase-2-induced cell growth through Akt phosphorylation was demonstrated in vitro. In chronic heart failure, left ventricular assist devices lead to hypertrophy regression and molecular changes. Therefore, the expression of cyclooxygenase-2, phosphorylated Akt (p-Akt), and p-Erk 1/2, as well as cardiac hypertrophy before and after left ventricular assist device insertion, was investigated.

Methods

In myocardial tissue before and after left ventricular assist device insertion, the expression of cyclooxygenase-2, p-Akt (Thr308), p-Akt (Ser473), and p-Erk 1/2 was demonstrated by immunohistochemistry and quantified by morphometry. Colocalization of cyclooxygenase-2 and p-Akt (Thr308) was investigated by immuno-doublestaining.

Results

A significant decrease of cyclooxygenase-2, p-Akt (Thr308), p-Akt (Ser473), and p-Erk 1/2 protein expression and hypertrophy regression was observed after left ventricular assist device insertion. A significant correlation between cyclooxygenase-2 and p-Akt (Thr308) expression, as well as between cyclooxygenase-2 expression and cardiomyocyte diameter, was observed before, but not after, left ventricular assist device insertion. Only cyclooxygenase-2-positive cardiomyocytes showed significant hypertrophy regression on unloading. Sarcoplasmic colocalization of cyclooxygenase-2 and p-Akt (Thr308) is present before left ventricular assist device insertion and is decreased after unloading, whereas the normal myocardium is completely devoid of it.

Conclusions

Left ventricular assist device treatment is associated with a significant decrease of cyclooxygenase-2, p-Akt (Thr308), p-Akt (Ser473), and p-Erk 1/2, and cardiac hypertrophy regression of cyclooxygenase-2-positive cardiomyocytes. The significant correlation and colocalization in cardiomyocytes of cyclooxygenase-2 and p-Akt (Thr308) before left ventricular assist device insertion suggests a cross-talk between the 2 molecules in the progression of cardiac hypertrophy, which is reversibly regulated by the left ventricular assist device.

CTSNet classification: 22, 27, 34

Abbreviations and Acronyms: CHF, chronic heart failure, COX, cyclooxygenase, LVAD, left ventricular assist device

 

 This study was supported by the Deutsche Forschungsgemeinschaft to H. A. Baba (Ba1730/9-1), C. Schmid, and C. Vahlhaus (Va156/5-2).

PII: S0022-5223(06)01701-6

doi:10.1016/j.jtcvs.2006.07.042

The Journal of Thoracic and Cardiovascular Surgery
Volume 133, Issue 1 , Pages 37-43, January 2007

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