The role of COX-2 in heart pathology

J. M. Streicher, Yibin Wang

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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 expdrimental 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 incardiac physiology and pathology.

Original languageEnglish (US)
Pages (from-to)69-79
Number of pages11
JournalCardiovascular and Hematological Agents in Medicinal Chemistry
Volume6
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

Keywords

  • COX-2
  • Cyclooxygenase
  • Genetic models
  • Heart failure
  • Molecular signaling
  • Pharmacologic inhibition

ASJC Scopus subject areas

  • Hematology
  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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