The role of COX-2 in heart pathology

• Published in: Cardiovascular & hematological agents in medicinal chemistry Vol. 6; no. 1; p. 69
• Main Authors: Streicher, J M, Wang, Y
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2008
• Subjects: Animals; Cyclooxygenase 2 - deficiency; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - therapeutic use; Disease Models, Animal; Heart Diseases - drug therapy; Heart Diseases - enzymology; Heart Diseases - genetics; Heart Diseases - pathology; Humans; Prostaglandins - metabolism; Signal Transduction
• ISSN: 1871-5257; 1875-6182
• DOI: 10.2174/187152508783329948

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.