Microsomal prostaglandin E2 synthase-1 deletion leads to adverse left ventricular remodeling after myocardial infarction

Norbert Degousee, Shafie Fazel, Denis Angoulvant, Eva Stefanski, Sven Christian Pawelzik, Marina Korotkova, Sara Arab, Peter Liu, Thomas F. Lindsay, Sun Zhuo, Jagdish Butany, Ren Ke Li, Laurent Audoly, Ronald Schmidt, Carlo Angioni, Gerd Geisslinger, Per Johan Jakobsson, Barry B. Rubin

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


BACKGROUND - Pharmacological inhibition of cyclooxygenase-2 increases the risk of myocardial infarction (MI) and stroke. Microsomal prostaglandin (PG) E2 synthase-1 (mPGES-1), encoded by the Ptges gene, functions downstream from cyclooxygenase-2 in the inducible PGE2 biosynthetic pathway. We caused acute MI in Ptges and Ptges mice to define the role of mPGES-1 in cardiac ischemic injury. METHODS AND RESULTS - Twenty-eight days after MI, Ptges mice develop more left ventricular (LV) dilation, have worse LV systolic and diastolic function, and have higher LV end-diastolic pressure than Ptges mice but have similar pulmonary wet-to-dry weight ratios, cardiac mass, infarct size, and mortality. The length-to-width ratio of individual cardiomyocytes is significantly greater in Ptges than Ptges mice after MI, a finding consistent with eccentric cardiomyocyte hypertrophy in Ptges mice. Expression of atrial natriuretic peptide, brain natriuretic peptide, and α- and β-myosin heavy chain, markers of ventricular hypertrophy, is higher in the LV of Ptges than Ptges mice after MI. Ptges mice express cyclooxygenase-2 and mPGES-1 protein in inflammatory cells adjacent to the infarct after MI but do not express these proteins in cardiomyocytes. Ptges mice express cyclooxygenase-2 in inflammatory cells adjacent to the infarct and do not express mPGES-1 in any cells in the heart. Levels of PGE2 but not PGD2, thromboxane A2, PGI2, or PGF2α are higher in the infarct and LV remote from the infarct after MI in Ptges than Ptges mice. CONCLUSIONS - In Ptges mice, mPGES-1 in inflammatory cells catalyzes PGE2 biosynthesis in the LV after MI. Deletion of mPGES-1 leads to eccentric cardiac myocyte hypertrophy, LV dilation, and impaired LV contractile function after acute MI.

Original languageEnglish (US)
Pages (from-to)1701-1710
Number of pages10
Issue number13
StatePublished - Apr 2008
Externally publishedYes


  • Hypertrophy
  • Inflammation
  • Myocardial infarction
  • Prostaglandins
  • Remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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