title: Prostaglandin E Receptor Subtype 4 Signaling in the Heart: Role in Ischemia/Reperfusion Injury and Cardiac Hypertrophy.
abstract: Prostaglandin E2 (PGE2) is an endogenous lipid mediator, produced from the metabolism of arachidonic acids, upon the sequential actions of phospholipase A2, cyclooxygenases, and prostaglandin E synthases. The various biological functions governed by PGE2 are mediated through its four distinct prostaglandin E receptors (EPs), designated as EP1, EP2, EP3, and EP4, among which the EP4 receptor is the one most widely distributed in the heart. The availability of global or cardiac-specific EP4 knockout mice and the development of selective EP4 agonists/antagonists have provided substantial evidence to support the role of EP4 receptor in the heart. However, like any good drama, activation of PGE2-EP4 signaling exerts both protective and detrimental effects in the ischemic heart disease. Thus, the primary object of this review is to provide a comprehensive overview of the current progress of the PGE2-EP4 signaling in ischemic heart diseases, including cardiac hypertrophy and myocardial ischemia/reperfusion injury. A better understanding of PGE2-EP4 signaling should promote the development of more effective therapeutic approaches to treat the ischemic heart diseases without triggering unwanted side effects.
authors.affiliation: Department of Anesthesiology, The First Hospital, Jilin University, Jilin 130021, China.
authors.forename: Lei
authors.identifier: 0000-0002-3265-3087
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Anesthesiology, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Yin
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Pharmacology and Pharmacy and State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Pokfulam, Hong Kong; School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Eva Hoi Ching
authors.initials: EH
authors.lastname: Tang
authors.affiliation: Department of Anesthesiology, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Michael G
authors.identifier: 0000-0001-5801-274X
authors.initials: MG
authors.lastname: Irwin
authors.affiliation: Department of Anesthesiology, The First Hospital, Jilin University, Jilin 130021, China.
authors.forename: Haichun
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Zhengyuan
authors.identifier: 0000-0002-7002-5524
authors.initials: Z
authors.lastname: Xia
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone