Abstract 1118: Microsomal Prostaglandin E2 Synthase-1 Regulates Cardiomyocyte Hypertrophy, Left Ventricular Remodeling and Left Ventricular Function after Acute Myocardial Infarction
Microsomal prostaglandin E2 synthase-1 (mPGES−1), encoded by the Ptges gene, is downstream from COX-2 in the inducible PGE2 biosynthetic pathway. Recently, we showed that mPGES−1 catalyzes the majority of PGE2 biosynthesis by cardiomyocytes. To define the role of mPGES−1 in cardiac ischemic injury we subjected Ptges+/+ and Ptges−/− mice (n ≈ 50 in each group) to left coronary artery (LCA) ligation, which causes acute myocardial infarction (MI). Twenty-eight days after MI, Ptges−/− mice had more dilated hearts and worse left ventricular systolic and diastolic function than Ptges+/+ mice (in situ perfusion fixation and morphometry, LV pressure conductance catheterization, 2-dimensional echocardiography, Table 1⇓). Cardiac mass, infarct size (Table 1⇓) extracellular matrix degradation and survival (not shown) were similar in Ptges+/+ and Ptges−/− mice after MI. In contrast, cardiomyocyte hypertrophy remote from the zone of infarction was impaired in Ptges−/− mice in comparison with Ptges+/+ mice 28 days after MI. Furthermore, cardiomyocytes from Ptges−/− mice had a greater length to width ratio than cardiomyocytes from Ptges+/+ mice (Table 1⇓), a finding consistent with maladaptive eccentric hypertrophy in Ptges−/− mice. mRNA levels of atrial and brain natriuretic peptide, which both negatively modulate cardiomyocyte hypertrophy, were 2.2 and 3.2-fold higher in cardiomyocytes remote from the zone of infarction in Ptges−/− mice in comparison with Ptges+/+ mice 3 days after MI (real-time PCR). These studies identify a novel linkage between mPGES-1 and adaptive cardiomyocyte hypertrophy, ventricular remodeling and maintenance of left ventricular systolic and diastolic function after acute MI.