Expression of dual Nucleotides/Cysteinyl‐Leukotrienes ReceptorGPR17 in early trafficking of cardiac stromal cells after myocardial infarction

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Abstract
GPR17 is a Gi‐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 ofGPR17 was investigated in mice before and at early stages after myocardial infarction by using immunofluorescence, flow cytometry andRT‐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 markerCD44.GPR17 function was investigatedin vitroin a Sca‐1+/CD31−cell line derived from normal hearts. These experiments showed a migratory function of the receptor by treatment withUDP‐glucose and leukotrieneLTD4, twoGPR17 pharmacological agonists. TheGPR17 function was finally assessedin vivoby treating infarcted mice withCangrelor, a pharmacological receptor antagonist, which, at least in part, inhibited early recruitment ofGPR17+andCD45+cells. These findings suggest a regulation of heart‐resident mesenchymal cells and blood‐borne cellular species recruitment following myocardial infarction, orchestrated byGPR17.

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