The role of COX-2 in heart pathology.
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.
Streicher
J M
JM
Department of Anesthesiology, Physiology and Medicine, Molecular Biology Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
Wang
Y
Y
D000818:Animals; D051546:Cyclooxygenase 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004195:Disease Models, Animal; D006331:Heart Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D011453:Prostaglandins / Q000378:metabolism; D015398:Signal Transduction
D052246:Cyclooxygenase 2 Inhibitors; D011453:Prostaglandins; D051546:Cyclooxygenase 2