Compensatory hypertrophy induced by ventricular cardiomyocyte-specific COX-2 expression in mice.
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.
Streicher
John M
JM
Department of Anesthesiology, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, USA.
Kamei
Kenichiro
K
Ishikawa
Tomo-o
TO
Herschman
Harvey
H
Wang
Yibin
Y
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology*; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007783:Lactones; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D013450:Sulfones
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human