%0 Journal Article %A Shuang Ji %A Rui Guo %A Jing Wang %A Lei Qian %A Min Liu %A Hu Xu %A Jiayang Zhang %A Youfei Guan %A Guangrui Yang %A Lihong Chen %T mPGES-1 deletion attenuates isoproterenol-induced myocardial fibrosis in mice %D 2020 %R 10.1124/jpet.120.000023 %J Journal of Pharmacology and Experimental Therapeutics %P JPET-AR-2020-000023 %X Deletion of microsomal PGE2 synthase-1 (mPGES-1) inhibits inflammation and protects against atherosclerotic vascular diseases, but displayed variable influence on pathological cardiac remodeling. Overactivation of β-adrenergic receptors (β-ARs) causes heart dysfunction and cardiac remodeling, while the role of mPGES-1 in β-ARs induced cardiac remodeling is unknown. Here we addressed this question using mPGES-1 knockout mice, and subjecting them to isoproterenol, a synthetic nonselective agonist for β-ARs, at 5mg/kg/day or 15mg/kg/day to induce different degrees of cardiac remodeling in vivo. Cardiac structure and function were assessed by echocardiography 24 hours after the last of seven consecutive daily injections of isoproterenol, and cardiac fibrosis was examined by Masson trichrome stain in morphology and by real-time PCR for the expression of fibrosis related genes. The results showed that deletion of mPGES-1 had no significant effect on isoproterenol-induced cardiac dysfunction or hypertrophy. However, the cardiac fibrosis was dramatically attenuated in the mPGES-1 knockout mice after either low dose or high dose isoproterenol exposure. Furthermore, in vitro study revealed that overexpression of mPGES-1 in cultured cardiac fibroblasts increased isoproterenol induced fibrosis, while knocking-down mPGES-1 in cardiac myocytes decreased the fibrogenesis of fibroblasts. In conclusion, mPGES-1 deletion protects against isoproterenol-induced cardiac fibrosis in mice, and targeting mPGES-1 may represent a novel strategy to attenuate pathological cardiac fibrosis, induced by β-ARs agonists. Significance Statement Inhibitors of mPGES-1 are being developed as alternative analgesics which are less likely to elicit cardiovascular hazards than COX-2 selective NSAIDs. We have demonstrated that deletion of mPGES-1 protects inflammatory vascular diseases and promotes post-MI survival. The role of mPGES-1 in β-adrenergic receptors induced cardiomyopathy is unknown. Here we illustrated that deletion of mPGES-1 alleviated isoproterenol-induced cardiac fibrosis without deteriorating cardiac dysfunction. These results illustrated that targeting mPGES-1 may represent an efficacious approach to the treatment of inflammatory cardiovascular diseases. %U https://jpet.aspetjournals.org/content/jpet/early/2020/08/05/jpet.120.000023.full.pdf