Abstract P2014: Knockout Of Prostaglandin E2 Ep3 Receptor Improves Cardiac Function In Both Sexes In A Mouse Model Of Myocardial Infarction

• Published in: Circulation research 2023-08, Vol.133 (Suppl_1)
• Main Authors: Bryson, Timothy D, Bhat, Shaheen Y, Taube, David, Xu, Jiang, Peterson, Edward, Harding, Pamela
• Format: Article
• Language: English
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/res.133.suppl_1.P2014

Abstract only Prostaglandin E 2 is an autacoid that acts through 4 G-protein-coupled receptors (EP1-EP4). We previously reported that expression of the EP3 receptor increases after myocardial infarction (MI) and mediates reduced cardiac function. This effect was exacerbated in mice that overexpress EP3 in the cardiomyocytes. Furthermore, we reported that the EP3 receptor antagonist, L798106 reduced blood pressure in the Angiotensin II hypertension model and improved cardiac function. We therefore hypothesized that cardiomyocyte specific knock-out of EP3 (EP3 KO) and/or pharmacological antagonism of EP3 protects the heart from cardiac dysfunction after MI. To test our hypothesis, we created a cardiomyocyte specific (αMHC promoter), tamoxifen inducible CM-EP3 KO mouse. Fifteen-week-old male and female EP3 KO and floxed controls underwent sham or MI surgery. After 2 wks, echocardiography was performed, and all statistical analysis was performed by a biostatistician at Henry Ford Health. There were no significant differences in cardiac function between strains after sham operation. After 2 wks MI, male floxed control mice showed significant reductions in ejection fraction (EF;68 ± 5.6 % sham vs 49.1 ± 5.2 % MI; p