Prostaglandin E Receptor Subtype 4 Signaling in the Heart: Role in Ischemia/Reperfusion Injury and Cardiac Hypertrophy

Figure 2

Schematic representation of the proposed role of EP4-mediated signaling under myocardial ischemia. During cardiac ischemia, increased PGE₂ level may be a consequence of increased hypoxia inducible factor- (HIF-) 1α/cyclooxygenase-2 (COX-2) activation. PGE₂ may play a beneficial role in cardiac ischemia/reperfusion injury through EP4/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) or EP4/signal transducer and activator of transcription 3 (Stat3) signaling pathway. In addition, synthesized PGE₂ in cardiomyocytes also diffuses into adjacent infiltrated macrophages or other inflammatory cells, protects the heart from ischemia/reperfusion injury through binding with EP4 receptor, and exerts anti-inflammatory effects.