Compensatory hypertrophy induced by ventricular cardiomyocyte-specific COX-2 expression in mice

Streicher, John M.; Kamei, Kenichiro; Ishikawa, Tomo-o; Herschman, Harvey; Wang, Yibin

doi:10.1016/j.yjmcc.2010.01.021

« Previous Next »Journal of Molecular and Cellular Cardiology
Volume 49, Issue 1 , Pages 88-94, July 2010

Compensatory hypertrophy induced by ventricular cardiomyocyte-specific COX-2 expression in mice

John M. Streicher
- Departments of Anesthesiology, Physiology and Medicine, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, USA
Kenichiro Kamei
- Biological Chemistry and Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, USA
Tomo-o Ishikawa
- Biological Chemistry and Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, USA
Harvey Herschman
- Biological Chemistry and Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, USA
- Molecular Biology Institute, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, USA
Yibin Wang
- Departments of Anesthesiology, Physiology and Medicine, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, USA
- Molecular Biology Institute, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, USA
- Corresponding author. 650 Charles E. Young Drive, Room 569, CHS, Department of Anesthesiology, David Geffen School of Medicine, UCLA, Los Angeles, CA 91301, USA. Tel.: +1 310 206 5197; fax: +1 310 206 5907.

Received 26 October 2009; received in revised form 29 January 2010; accepted 30 January 2010. published online 18 February 2010.

Abstract

Cyclooxygenase-2 (COX-2) is an important mediator of inflammation in stress and disease states. Recent attention has focused on the role of COX-2 in human heart failure and diseases owing to the finding that highly specific COX-2 inhibitors (i.e., Vioxx) increased the risk of myocardial infarction and stroke in chronic users. However, the specific impact of COX-2 expression in the intact heart remains to be determined. We report here the development of a transgenic mouse model, using a loxP-Cre approach, which displays robust COX-2 overexpression and subsequent prostaglandin synthesis specifically in ventricular myocytes. Histological, functional, and molecular analyses showed that ventricular myocyte specific COX-2 overexpression led to cardiac hypertrophy and fetal gene marker activation, but with preserved cardiac function. Therefore, specific induction of COX-2 and prostaglandin in vivo is sufficient to induce compensated hypertrophy and molecular remodeling.

Keywords: Cyclooxygenase, COX-2, Transgenic, Hypertrophy, Compensatory