TABLE 1

Reported roles of EP4-mediated signaling pathways in the cardiovascular system

Tissues/CellsReported FunctionsProposed Effector Pathway(s)Pathophysiologic ProcessReferences
HeartCardiomyocyte hypertrophyEGFR activation; ERK1/2Protein synthesisMendez and LaPointe, 2005
Cardiomyocyte hypertrophyERK1/2; STAT3Protein synthesisFrias et al, 2007; Qian et al., 2008
Cardiomyocyte hypertrophyPKA; Rap; ERK1/2;p90RSKc-Fos and BNP expressionHe et al., 2010
Reduced infarct sizeN.D.N.D.Xiao et al., 2004
Reduced infarct sizeN.D.Inhibition of MCP-1 production and recruitment of macrophagesHishikari et al., 2009
Prolonged graft survivalN.D.Inhibition of NF-κB and cytokine productionOgawa et al., 2009
Suppressed autoimmune myocarditisN.D.Inhibition of T-cell proliferation and MCP-1 productionNgoc et al., 2011
Ductus arteriosusVasodilationcAMP; AC6Phosphorylation of vasodilator-stimulated phosphoproteinYokoyama et al., 2010b
VasodilationN.D.N.D.Smith et al., 1994; Kajino et al., 2004; Momma et al., 2005a,b
Intimal thickeningcAMP; AC6; PKA;p38 MAPKHyaluronan-mediated smooth muscle cell migrationYokoyama et al., 2006, 2010a
Renal arteryVasodilationcAMPDecreased intracellular calcium concentrationPurdy and Arendshorst, 2000
Saphenous veinVasodilationN.D.N.D.Coleman et al., 1994a; Rouaud et al., 1999; Jones and Chan, 2001; Wilson and Giles, 2005
Pulmonary veinVasodilationN.D.N.D.Walch et al., 1999; Foudi et al., 2008
Cerebral arteryVasodilationN.D.N.D.Davis et al., 2004; Maubach et al., 2009
Uterine arteryVasodilationN.D.N.D.Baxter et al., 1995
Endothelial cellsAngiogenesiscAMP; PKAγ;Rap1AeNOS activationZhang and Daaka, 2011
AngiogenesisN.D.eNOS activation; AMP activated protein kinase activationZhu et al., 2011
AngiogenesiscAMP; ERK1/2Endothelial cell migrationRao et al., 2007
AngiogenesisN.D.Endothelial cell migrationKuwano et al., 2004
AngiogenesisN.D.VEGF production; endothelial cell proliferationYanni et al., 2009
AtherosclerosisIncreased early atherosclerosisPI3K; AktInhibition of macrophage apoptosisBabaev et al., 2008
Proteolytic activationN.D.MMP-2 and MMP-9 activation in macrophagesCipollone et al., 2005
Inhibition of inflammationN.D.Inhibition of MCP-1 and IFN-γ-inducible protein 10 productionTang et al., 2011a
Aortic aneurysmProgression of aortic aneurysmN.D.Inhibition of IL-6 production and MMP-2 activationYokoyama et al., 2012
Progression of aortic aneurysmN.D.Inhibition of MMP-2 and MMP-9 activationCao et al., 2012
Inhibition of aortic aneurysmN.D.Inhibition of MCP-1 in macrophagesTang et al., 2011b

  • BNP, brain natriuretic peptide; eNOS, endothelial nitric-oxide synthase; N.D., not determined.