Arizona Health Sciences

The role of COX-2 in heart pathology.

TitleThe role of COX-2 in heart pathology.
Publication TypeJournal Article
Year of Publication2008
AuthorsStreicher JM, Wang Y
JournalCardiovasc Hematol Agents Med Chem
Volume6
Issue1
Pagination69-79
Date Published2008 Jan
ISSN1871-5257
KeywordsAnimals, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Disease Models, Animal, Heart Diseases, Humans, Prostaglandins, Signal Transduction
Abstract

Cyclooxygenase-2 (COX-2) is a key enzyme in the production of prostaglandins, and an important anti-inflammation drug target. Recent focus has been placed on the role of COX-2 in heart function and pathology, due to the finding that specific COX-2 inhibitors significantly increased the risk of heart disease in chronic users. However, the exact role of COX-2 in cardiac physiology and disease remains controversial due to the conflicting data reported. Roughly equal numbers of reports have shown either a detrimental role or a protective role for COX-2 in heart in experimental models. Here we attempt to provide a background on the more general roles of COX-2 in pathophysiology, as well as molecular mechanisms employed to control COX-2 expression. This background provides a basis for better understanding the functional role of COX-2 in human heart pathologies, based on the results of COX-2 pharmacological inhibitor studies in humans as well as COX-2 expression in human heart disease. Furthermore, we will explore the experimental evidence implicating different intracellular molecular signaling cascades that regulate COX-2 expression in cardiomyocytes. All of this data permits a more mechanistic understanding of the published studies using pharmacological inhibitors of COX-2 in experimental models of heart pathology. Lastly, we will examine the use of genetic manipulation of COX-2 in mice as one of the future avenues in an attempt to resolve the role of COX-2 in cardiac physiology and pathology.

Alternate JournalCardiovasc Hematol Agents Med Chem
PubMed ID18220723
Faculty Member Reference: 
John M. Streicher, PhD