Arizona Health Sciences

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

TitleCompensatory hypertrophy induced by ventricular cardiomyocyte-specific COX-2 expression in mice.
Publication TypeJournal Article
Year of Publication2010
AuthorsStreicher JM, Kamei K, Ishikawa T-O, Herschman H, Wang Y
JournalJ Mol Cell Cardiol
Volume49
Issue1
Pagination88-94
Date Published2010 Jul
ISSN1095-8584
KeywordsAnimals, Cardiomegaly, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Heart Failure, Heart Ventricles, Hypertrophy, Lactones, Mice, Mice, Transgenic, Myocardial Infarction, Myocytes, Cardiac, Sulfones
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.

DOI10.1016/j.yjmcc.2010.01.021
Alternate JournalJ. Mol. Cell. Cardiol.
PubMed ID20170663
PubMed Central IDPMC2883637
Grant ListR01 HL108186 / HL / NHLBI NIH HHS / United States
R01 CA084572 / CA / NCI NIH HHS / United States
P01 HL080111 / HL / NHLBI NIH HHS / United States
R01 HL103205 / HL / NHLBI NIH HHS / United States
HL70079 / HL / NHLBI NIH HHS / United States
P01 HL080111-050003 / HL / NHLBI NIH HHS / United States
HL62311 / HL / NHLBI NIH HHS / United States
R01 HL070079 / HL / NHLBI NIH HHS / United States
R01 HL062311 / HL / NHLBI NIH HHS / United States
R01 HL062311-09 / HL / NHLBI NIH HHS / United States
CA084572 / CA / NCI NIH HHS / United States
R01 HL062311-05 / HL / NHLBI NIH HHS / United States
Faculty Member Reference: 
John M. Streicher, PhD