TY - JOUR
T1 - Microsomal prostaglandin E2 synthase-1 deletion leads to adverse left ventricular remodeling after myocardial infarction
AU - Degousee, Norbert
AU - Fazel, Shafie
AU - Angoulvant, Denis
AU - Stefanski, Eva
AU - Pawelzik, Sven Christian
AU - Korotkova, Marina
AU - Arab, Sara
AU - Liu, Peter
AU - Lindsay, Thomas F.
AU - Zhuo, Sun
AU - Butany, Jagdish
AU - Li, Ren Ke
AU - Audoly, Laurent
AU - Schmidt, Ronald
AU - Angioni, Carlo
AU - Geisslinger, Gerd
AU - Jakobsson, Per Johan
AU - Rubin, Barry B.
PY - 2008/4
Y1 - 2008/4
N2 - 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.
AB - 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.
KW - Hypertrophy
KW - Inflammation
KW - Myocardial infarction
KW - Prostaglandins
KW - Remodeling
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U2 - 10.1161/CIRCULATIONAHA.107.749739
DO - 10.1161/CIRCULATIONAHA.107.749739
M3 - Article
C2 - 18347209
AN - SCOPUS:41649119130
SN - 0009-7322
VL - 117
SP - 1701
EP - 1710
JO - Circulation
JF - Circulation
IS - 13
ER -