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

Jeremias Wohlschlaeger1, Klaus Jürgen Schmitz, Jenci Palatty

  • 1Department of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Germany.

The Journal of Thoracic and Cardiovascular Surgery
|January 3, 2007
PubMed
Abstract

Insights

Left ventricular assist device (LVAD) treatment reduces cyclooxygenase-2 (COX-2) and phosphorylated Akt (p-Akt) in cardiac hypertrophy. Unloading via LVAD reverses COX-2 and p-Akt expression, suggesting their role in heart failure progression.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Heart Failure Pathophysiology

Background:

  • Cyclooxygenase-2 (COX-2) is implicated in cardiac hypertrophy during chronic heart failure.
  • The PI3K/Akt pathway regulates COX-2, with COX-2-induced cell growth observed in vitro.
  • Left ventricular assist devices (LVADs) promote hypertrophy regression and molecular changes in chronic heart failure.

Purpose of the Study:

  • To investigate the expression of COX-2, phosphorylated Akt (p-Akt), and p-Erk 1/2 in myocardial tissue.
  • To assess cardiac hypertrophy before and after LVAD insertion.
  • To explore the correlation and colocalization of COX-2 and p-Akt in the context of cardiac hypertrophy and LVAD treatment.

Main Methods:

  • Immunohistochemistry and morphometry were used to quantify COX-2, p-Akt (Thr308), p-Akt (Ser473), and p-Erk 1/2 expression in myocardial tissue.
  • Immuno-doublestaining was employed to investigate the colocalization of COX-2 and p-Akt (Thr308).
  • Analysis was performed on myocardial samples obtained before and after LVAD insertion.

Main Results:

  • LVAD insertion led to a significant decrease in COX-2, p-Akt, and p-Erk 1/2 expression, alongside hypertrophy regression.
  • A significant correlation between COX-2 and p-Akt (Thr308) was observed before LVAD insertion, but not after.
  • Only COX-2-positive cardiomyocytes exhibited significant hypertrophy regression upon unloading, with sarcoplasmic colocalization of COX-2 and p-Akt (Thr308) decreasing post-LVAD.

Conclusions:

  • LVAD treatment significantly reduces COX-2, p-Akt, and p-Erk 1/2, correlating with cardiac hypertrophy regression in COX-2-positive cardiomyocytes.
  • The observed correlation and colocalization of COX-2 and p-Akt (Thr308) before LVAD insertion suggest their interaction in cardiac hypertrophy progression.
  • These molecular changes are reversibly regulated by LVAD treatment, highlighting a potential therapeutic target.

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