The role of COX-2 in heart pathology

Cardiovasc Hematol Agents Med Chem. 2008 Jan;6(1):69-79. doi: 10.2174/187152508783329948.

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.

Publication types

  • Review

MeSH terms

  • 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

Substances

  • Cyclooxygenase 2 Inhibitors
  • Prostaglandins
  • Cyclooxygenase 2