title: Expression of dual nucleotides/cysteinyl-leukotrienes receptor GPR17 in early trafficking of cardiac stromal cells after myocardial infarction.
abstract: GPR17 is a G(i) -coupled dual receptor activated by uracil-nucleotides and cysteinyl-leukotrienes. These mediators are massively released into hypoxic tissues. In the normal heart, GPR17 expression has been reported. By contrast, its role in myocardial ischaemia has not yet been assessed. In the present report, the expression of GPR17 was investigated in mice before and at early stages after myocardial infarction by using immunofluorescence, flow cytometry and RT-PCR. Before induction of ischaemia, results indicated the presence of the receptor in a population of stromal cells expressing the stem-cell antigen-1 (Sca-1). At early stages after ligation of the coronary artery, the receptor was expressed in Sca-1(+) cells, and cells stained with Isolectin-B4 and anti-CD45 antibody. GPR17(+) cells also expressed mesenchymal marker CD44. GPR17 function was investigated in vitro in a Sca-1(+)/CD31(-) cell line derived from normal hearts. These experiments showed a migratory function of the receptor by treatment with UDP-glucose and leukotriene LTD4, two GPR17 pharmacological agonists. The GPR17 function was finally assessed in vivo by treating infarcted mice with Cangrelor, a pharmacological receptor antagonist, which, at least in part, inhibited early recruitment of GPR17(+) and CD45(+) cells. These findings suggest a regulation of heart-resident mesenchymal cells and blood-borne cellular species recruitment following myocardial infarction, orchestrated by GPR17.
authors.affiliation: Laboratorio di Biologia e Biochimica dell'Aterotrombosi, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Cosentino
authors.forename: Laura
authors.initials: L
authors.lastname: Castiglioni
authors.forename: Francesca
authors.initials: F
authors.lastname: Colazzo
authors.forename: Elena
authors.initials: E
authors.lastname: Nobili
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rosa
authors.forename: Maria P
authors.initials: MP
authors.lastname: Abbracchio
authors.forename: Luigi
authors.initials: L
authors.lastname: Sironi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pesce
mesh_terms: D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002465:Cell Movement; D018960:Hyaluronan Receptors; D017493:Leukocyte Common Antigens / Q000378:metabolism; D017998:Leukotriene D4 / Q000494:pharmacology / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000378:metabolism*; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D014532:Uridine Diphosphate Glucose / Q000494:pharmacology / Q000502:physiology
chemical_list: D000950:Antigens, Ly; C476399:Cd44 protein, mouse; C534979:GPR17 protein, mouse; D018960:Hyaluronan Receptors; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D058921:Purinergic P2Y Receptor Antagonists; D043562:Receptors, G-Protein-Coupled; D000249:Adenosine Monophosphate; C117446:cangrelor; D017998:Leukotriene D4; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; D014532:Uridine Diphosphate Glucose
keywords: Cysteinyl-Leukotrienes; GPR17; cardiac stromal cell; myocardial ischaemia; myofibroblasts