Cardiovascular biology of microsomal prostaglandin E synthase-1

Trends Cardiovasc Med. 2010 Aug;20(6):189-95. doi: 10.1016/j.tcm.2011.04.002.


Both traditional and purpose-designed nonsteroidal anti-inflammatory drugs, selective for inhibition of cyclooxygenase (COX)-2, alleviate pain and inflammation but confer a cardiovascular hazard attributable to inhibition of COX-2-derived prostacyclin (PGI(2)). Deletion of microsomal PGE synthase-1 (mPGES-1), the dominant enzyme that converts the COX-derived intermediate product PGH(2) to PGE(2), modulates inflammatory pain in rodents. In contrast with COX-2 deletion or inhibition, PGI(2) formation is augmented in mPGES-1(-/-) mice-an effect that may confer cardiovascular benefit but may undermine the analgesic potential of inhibitors of this enzyme. This review considers the cardiovascular biology of mPGES1 and the complex challenge of developing inhibitors of this enzyme.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Cardiovascular Diseases / enzymology*
  • Cardiovascular Diseases / pathology
  • Disease Models, Animal
  • Endothelium, Vascular / enzymology
  • Humans
  • Inflammation
  • Intramolecular Oxidoreductases / antagonists & inhibitors
  • Intramolecular Oxidoreductases / drug effects*
  • Neointima / enzymology
  • Prostaglandin-E Synthases


  • Anti-Inflammatory Agents, Non-Steroidal
  • Intramolecular Oxidoreductases
  • PTGES protein, human
  • Prostaglandin-E Synthases
  • Ptges protein, mouse