{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:33:26Z","timestamp":1792226006995,"version":"4.4.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Two distinct monocyte (Mo)\/macrophage (Mp) subsets (Ly6C<jats:sup>low<\/jats:sup> and Ly6C<jats:sup>high<\/jats:sup>) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E<jats:sub>2<\/jats:sub> is involved in the Mo\/Mp-mediated inflammatory response, however, the role of its receptors in Mos\/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the <jats:italic>Ep3<\/jats:italic> receptor in mice suppresses accumulation of Ly6C<jats:sup>low<\/jats:sup> Mos\/Mps in infarcted hearts. <jats:italic>Ep3<\/jats:italic> deletion in Mos\/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos\/Mps by suppressing TGF\u03b21 signalling and subsequently inhibits Ly6C<jats:sup>low<\/jats:sup> Mos\/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos\/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE<jats:sub>2<\/jats:sub>\/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6C<jats:sup>low<\/jats:sup> Mos\/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.<\/jats:p>","DOI":"10.1038\/ncomms14656","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T10:10:35Z","timestamp":1488535835000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction"],"prefix":"10.1038","volume":"8","author":[{"given":"Juan","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangyou","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guizhu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengkai","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-4474","authenticated-orcid":false,"given":"Michael","family":"Lazarus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,3]]},"reference":[{"key":"BFncomms14656_CR1","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1161\/ATVBAHA.114.304652","volume":"35","author":"P Dutta","year":"2015","unstructured":"Dutta, P. & Nahrendorf, M. Monocytes in myocardial infarction. Arterioscler., Thromb., Vasc. Biol. 35, 1066\u20131070 (2015).","journal-title":"Arterioscler., Thromb., Vasc. Biol."},{"key":"BFncomms14656_CR2","doi-asserted-by":"publisher","first-page":"818","DOI":"10.2353\/ajpath.2007.060547","volume":"170","author":"MJ van Amerongen","year":"2007","unstructured":"van Amerongen, M. J., Harmsen, M. C., van Rooijen, N., Petersen, A. H. & van Luyn, M. J. Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice. Am. J. Pathol. 170, 818\u2013829 (2007).","journal-title":"Am. J. Pathol."},{"key":"BFncomms14656_CR3","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1096\/fj.12-214049","volume":"27","author":"S Frantz","year":"2013","unstructured":"Frantz, S. et al. Monocytes\/macrophages prevent healing defects and left ventricular thrombus formation after myocardial infarction. FASEB J. 27, 871\u2013881 (2013).","journal-title":"FASEB J."},{"key":"BFncomms14656_CR4","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1161\/CIRCULATIONAHA.106.646091","volume":"115","author":"NG Frangogiannis","year":"2007","unstructured":"Frangogiannis, N. G. et al. Critical role of monocyte chemoattractant protein-1\/CC chemokine ligand 2 in the pathogenesis of ischemic cardiomyopathy. Circulation 115, 584\u2013592 (2007).","journal-title":"Circulation"},{"key":"BFncomms14656_CR5","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1161\/01.RES.0000246113.82111.2d","volume":"99","author":"H Morimoto","year":"2006","unstructured":"Morimoto, H. et al. Cardiac overexpression of monocyte chemoattractant protein-1 in transgenic mice prevents cardiac dysfunction and remodeling after myocardial infarction. Circ. Res. 99, 891\u2013899 (2006).","journal-title":"Circ. Res."},{"key":"BFncomms14656_CR6","doi-asserted-by":"publisher","first-page":"3037","DOI":"10.1084\/jem.20070885","volume":"204","author":"M Nahrendorf","year":"2007","unstructured":"Nahrendorf, M. et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J. Exp. Med. 204, 3037\u20133047 (2007).","journal-title":"J. Exp. Med."},{"key":"BFncomms14656_CR7","doi-asserted-by":"publisher","first-page":"4410","DOI":"10.4049\/jimmunol.172.7.4410","volume":"172","author":"C Sunderkotter","year":"2004","unstructured":"Sunderkotter, C. et al. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J. Immunol. 172, 4410\u20134417 (2004).","journal-title":"J. Immunol."},{"key":"BFncomms14656_CR8","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.immuni.2012.12.001","volume":"38","author":"S Yona","year":"2013","unstructured":"Yona, S. et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38, 79\u201391 (2013).","journal-title":"Immunity"},{"key":"BFncomms14656_CR9","doi-asserted-by":"publisher","first-page":"5695","DOI":"10.4049\/jimmunol.1301445","volume":"191","author":"T Varga","year":"2013","unstructured":"Varga, T. et al. Tissue LyC6-macrophages are generated in the absence of circulating LyC6- monocytes and Nur77 in a model of muscle regeneration. J. Immunol. 191, 5695\u20135701 (2013).","journal-title":"J. Immunol."},{"key":"BFncomms14656_CR10","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1161\/CIRCRESAHA.114.303204","volume":"114","author":"I Hilgendorf","year":"2014","unstructured":"Hilgendorf, I. et al. Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium. Circ. Res. 114, 1611\u20131622 (2014).","journal-title":"Circ. Res."},{"key":"BFncomms14656_CR11","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1016\/j.jacc.2009.08.089","volume":"55","author":"P Panizzi","year":"2010","unstructured":"Panizzi, P. et al. Impaired infarct healing in atherosclerotic mice with Ly-6C(hi) monocytosis. J. Am. Coll. Cardiol. 55, 1629\u20131638 (2010).","journal-title":"J. Am. Coll. Cardiol."},{"key":"BFncomms14656_CR12","doi-asserted-by":"publisher","first-page":"e0120739","DOI":"10.1371\/journal.pone.0120739","volume":"10","author":"DK Singla","year":"2015","unstructured":"Singla, D. K., Singla, R. D., Abdelli, L. S. & Glass, C. Fibroblast growth factor-9 enhances M2 macrophage differentiation and attenuates adverse cardiac remodeling in the infarcted diabetic heart. PLoS ONE 10, e0120739 (2015).","journal-title":"PLoS ONE"},{"key":"BFncomms14656_CR13","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1177\/1074248414534916","volume":"20","author":"T Ben-Mordechai","year":"2015","unstructured":"Ben-Mordechai, T. et al. Targeting macrophage subsets for infarct repair. J. Cardiovasc. Pharmacol. Ther. 20, 36\u201351 (2015).","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"BFncomms14656_CR14","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/j.bbalip.2014.07.008","volume":"1851","author":"K Kawahara","year":"2015","unstructured":"Kawahara, K., Hohjoh, H., Inazumi, T., Tsuchiya, S. & Sugimoto, Y. Prostaglandin E2-induced inflammation: relevance of prostaglandin E receptors. Biochim. Biophys. Acta 1851, 414\u2013421 (2015).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFncomms14656_CR15","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.tcm.2011.04.002","volume":"20","author":"M Wang","year":"2010","unstructured":"Wang, M. & FitzGerald, G. A. Cardiovascular biology of microsomal prostaglandin E synthase-1. Trends Cardiovasc. Med. 20, 189\u2013195 (2010).","journal-title":"Trends Cardiovasc. Med."},{"key":"BFncomms14656_CR16","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1161\/CIRCULATIONAHA.107.749739","volume":"117","author":"N Degousee","year":"2008","unstructured":"Degousee, N. et al. Microsomal prostaglandin E2 synthase-1 deletion leads to adverse left ventricular remodeling after myocardial infarction. Circulation 117, 1701\u20131710 (2008).","journal-title":"Circulation"},{"key":"BFncomms14656_CR17","doi-asserted-by":"publisher","first-page":"2904","DOI":"10.1161\/CIRCULATIONAHA.112.099754","volume":"125","author":"N Degousee","year":"2012","unstructured":"Degousee, N. et al. Lack of microsomal prostaglandin E(2) synthase-1 in bone marrow-derived myeloid cells impairs left ventricular function and increases mortality after acute myocardial infarction. Circulation 125, 2904\u20132913 (2012).","journal-title":"Circulation"},{"key":"BFncomms14656_CR18","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1093\/cvr\/cvu062","volume":"102","author":"S Van Linthout","year":"2014","unstructured":"Van Linthout, S., Miteva, K. & Tschope, C. Crosstalk between fibroblasts and inflammatory cells. Cardiovasc. Res. 102, 258\u2013269 (2014).","journal-title":"Cardiovasc. Res."},{"key":"BFncomms14656_CR19","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1172\/JCI77656","volume":"125","author":"A Lu","year":"2015","unstructured":"Lu, A. et al. EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho\/TGF-beta1 signaling. J. Clin. Invest. 125, 1228\u20131242 (2015).","journal-title":"J. Clin. Invest."},{"key":"BFncomms14656_CR20","doi-asserted-by":"publisher","first-page":"e10","DOI":"10.1182\/blood-2009-07-235028","volume":"115","author":"MA Ingersoll","year":"2010","unstructured":"Ingersoll, M. A. et al. Comparison of gene expression profiles between human and mouse monocyte subsets. Blood 115, e10\u2013e19 (2010).","journal-title":"Blood"},{"key":"BFncomms14656_CR21","doi-asserted-by":"publisher","first-page":"21","DOI":"10.4049\/jimmunol.1101029","volume":"188","author":"P Kalinski","year":"2012","unstructured":"Kalinski, P. Regulation of immune responses by prostaglandin E2. J. Immunol. 188, 21\u201328 (2012).","journal-title":"J. Immunol."},{"key":"BFncomms14656_CR22","doi-asserted-by":"publisher","first-page":"2654","DOI":"10.1161\/CIRCULATIONAHA.109.910687","volume":"121","author":"Y Hui","year":"2010","unstructured":"Hui, Y. et al. Targeted deletions of cyclooxygenase-2 and atherogenesis in mice. Circulation 121, 2654\u20132660 (2010).","journal-title":"Circulation"},{"key":"BFncomms14656_CR23","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.4049\/jimmunol.1100889","volume":"187","author":"M Heusinkveld","year":"2011","unstructured":"Heusinkveld, M. et al. M2 macrophages induced by prostaglandin E2 and IL-6 from cervical carcinoma are switched to activated M1 macrophages by CD4+ Th1 cells. J. Immunol. 187, 1157\u20131165 (2011).","journal-title":"J. Immunol."},{"key":"BFncomms14656_CR24","doi-asserted-by":"publisher","first-page":"11712","DOI":"10.1073\/pnas.0701700104","volume":"104","author":"CL Weller","year":"2007","unstructured":"Weller, C. L. et al. Chemotactic action of prostaglandin E2 on mouse mast cells acting via the PGE2 receptor 3. Proc. Natl Acad. Sci. USA 104, 11712\u201311717 (2007).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms14656_CR25","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1146\/annurev.pharmtox.41.1.661","volume":"41","author":"RM Breyer","year":"2001","unstructured":"Breyer, R. M., Bagdassarian, C. K., Myers, S. A. & Breyer, M. D. Prostanoid receptors: subtypes and signaling. Annu. Rev. Pharmacol. Toxicol. 41, 661\u2013690 (2001).","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"BFncomms14656_CR26","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1161\/CIRCRESAHA.113.301033","volume":"113","author":"J Zhang","year":"2013","unstructured":"Zhang, J. et al. Cyclooxygenase-2-derived prostaglandin E(2) promotes injury-induced vascular neointimal hyperplasia through the E-prostanoid 3 receptor. Circ. Res. 113, 104\u2013114 (2013).","journal-title":"Circ. Res."},{"key":"BFncomms14656_CR27","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1182\/blood-2008-07-170787","volume":"113","author":"L Landsman","year":"2009","unstructured":"Landsman, L. et al. CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival. Blood 113, 963\u2013972 (2009).","journal-title":"Blood"},{"key":"BFncomms14656_CR28","doi-asserted-by":"publisher","first-page":"5035","DOI":"10.1172\/JCI71307","volume":"123","author":"MS Lionakis","year":"2013","unstructured":"Lionakis, M. S. et al. CX3CR1-dependent renal macrophage survival promotes Candida control and host survival. J. Clin. Invest. 123, 5035\u20135051 (2013).","journal-title":"J. Clin. Invest."},{"key":"BFncomms14656_CR29","doi-asserted-by":"publisher","first-page":"2797","DOI":"10.4049\/jimmunol.1403209","volume":"195","author":"X Peng","year":"2015","unstructured":"Peng, X., Zhang, J., Xiao, Z., Dong, Y. & Du, J. CX3CL1-CX3CR1 interaction increases the population of Ly6C-CX3CR1hi macrophages contributing to unilateral ureteral obstruction-induced fibrosis. J. Immunol. 195, 2797\u20132805 (2015).","journal-title":"J. Immunol."},{"key":"BFncomms14656_CR30","doi-asserted-by":"publisher","first-page":"150","DOI":"10.3389\/fncel.2015.00150","volume":"9","author":"T Kaur","year":"2015","unstructured":"Kaur, T., Hirose, K., Rubel, E. W. & Warchol, M. E. Macrophage recruitment and epithelial repair following hair cell injury in the mouse utricle. Front. Cell. Neurosci. 9, 150 (2015).","journal-title":"Front. Cell. Neurosci."},{"key":"BFncomms14656_CR31","doi-asserted-by":"publisher","first-page":"569","DOI":"10.4049\/jimmunol.180.1.569","volume":"180","author":"Y Ishida","year":"2008","unstructured":"Ishida, Y., Gao, J. L. & Murphy, P. M. Chemokine receptor CX3CR1 mediates skin wound healing by promoting macrophage and fibroblast accumulation and function. J. Immunol. 180, 569\u2013579 (2008).","journal-title":"J. Immunol."},{"key":"BFncomms14656_CR32","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1016\/j.burns.2011.08.001","volume":"37","author":"AJ Clover","year":"2011","unstructured":"Clover, A. J., Kumar, A. H. & Caplice, N. M. Deficiency of CX3CR1 delays burn wound healing and is associated with reduced myeloid cell recruitment and decreased sub-dermal angiogenesis. Burns 37, 1386\u20131393 (2011).","journal-title":"Burns"},{"key":"BFncomms14656_CR33","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1096\/fj.14-270090","volume":"30","author":"W Zhao","year":"2015","unstructured":"Zhao, W., Lu, H., Wang, X., Ransohoff, R. M. & Zhou, L. CX3CR1 deficiency delays acute skeletal muscle injury repair by impairing macrophage functions. FASEB J. 30, 380\u2013393 (2015).","journal-title":"FASEB J."},{"key":"BFncomms14656_CR34","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1189\/jlb.0806517","volume":"81","author":"SH Jeon","year":"2007","unstructured":"Jeon, S. H. et al. Mechanisms underlying TGF-beta1-induced expression of VEGF and Flk-1 in mouse macrophages and their implications for angiogenesis. J. Leukoc. Biol. 81, 557\u2013566 (2007).","journal-title":"J. Leukoc. Biol."},{"key":"BFncomms14656_CR35","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1006\/jmcc.1999.1072","volume":"32","author":"T Hohlfeld","year":"2000","unstructured":"Hohlfeld, T., Meyer-Kirchrath, J., Vogel, Y. C. & Schror, K. Reduction of infarct size by selective stimulation of prostaglandin EP(3)receptors in the reperfused ischemic pig heart. J. Mol. Cell. Cardiol. 32, 285\u2013296 (2000).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"BFncomms14656_CR36","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1161\/01.ATV.19.9.2141","volume":"19","author":"K Zacharowski","year":"1999","unstructured":"Zacharowski, K. et al. Selective activation of the prostanoid EP(3) receptor reduces myocardial infarct size in rodents. Arterioscler., Thromb, Vasc. Biol. 19, 2141\u20132147 (1999).","journal-title":"Arterioscler., Thromb, Vasc. Biol."},{"key":"BFncomms14656_CR37","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1038\/sj.bjp.0702348","volume":"126","author":"K Zacharowski","year":"1999","unstructured":"Zacharowski, K., Olbrich, A., Otto, M., Hafner, G. & Thiemermann, C. Effects of the prostanoid EP3-receptor agonists M&B 28767 and GR 63799X on infarct size caused by regional myocardial ischaemia in the anaesthetized rat. Br. J. Pharmacol. 126, 849\u2013858 (1999).","journal-title":"Br. J. Pharmacol."},{"key":"BFncomms14656_CR38","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1161\/CIRCULATIONAHA.104.508333","volume":"112","author":"M Martin","year":"2005","unstructured":"Martin, M. et al. Cardiospecific overexpression of the prostaglandin EP3 receptor attenuates ischemia-induced myocardial injury. Circulation 112, 400\u2013406 (2005).","journal-title":"Circulation"},{"key":"BFncomms14656_CR39","doi-asserted-by":"publisher","first-page":"3009","DOI":"10.1073\/pnas.0611209104","volume":"104","author":"M Sanchez-Alavez","year":"2007","unstructured":"Sanchez-Alavez, M. et al. Night eating and obesity in the EP3R-deficient mouse. Proc. Natl Acad. Sci. USA 104, 3009\u20133014 (2007).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms14656_CR40","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1210\/en.2015-1693","volume":"157","author":"RP Ceddia","year":"2016","unstructured":"Ceddia, R. P. et al. The PGE2 EP3 receptor regulates diet-induced adiposity in male mice. Endocrinology 157, 220\u2013232 (2016).","journal-title":"Endocrinology"},{"key":"BFncomms14656_CR41","doi-asserted-by":"crossref","unstructured":"Yan, S. et al. Prostaglandin E2 promotes hepatic bile acid synthesis by an E prostanoid receptor 3-mediated hepatocyte nuclear receptor 4\u03b1\/cholesterol 7\u03b1-hydroxylase pathway in mice. Hepatology doi: 10.1002\/hep.28928 (2016).","DOI":"10.1002\/hep.28928"},{"key":"BFncomms14656_CR42","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","volume":"31","author":"E Ricciotti","year":"2011","unstructured":"Ricciotti, E. & FitzGerald, G. A. Prostaglandins and inflammation. Arterioscler., Thromb, Vasc. Biol. 31, 986\u20131000 (2011).","journal-title":"Arterioscler., Thromb, Vasc. Biol."},{"key":"BFncomms14656_CR43","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1084\/jem.20061617","volume":"204","author":"S Gross","year":"2007","unstructured":"Gross, S., Tilly, P., Hentsch, D., Vonesch, J. L. & Fabre, J. E. Vascular wall-produced prostaglandin E2 exacerbates arterial thrombosis and atherothrombosis through platelet EP3 receptors. J. Exp. Med. 204, 311\u2013320 (2007).","journal-title":"J. Exp. Med."},{"key":"BFncomms14656_CR44","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1038\/nn1949","volume":"10","author":"M Lazarus","year":"2007","unstructured":"Lazarus, M. et al. EP3 prostaglandin receptors in the median preoptic nucleus are critical for fever responses. Nat. Neurosci. 10, 1131\u20131133 (2007).","journal-title":"Nat. Neurosci."},{"key":"BFncomms14656_CR45","first-page":"349","volume":"38","author":"B Stapel","year":"2016","unstructured":"Stapel, B. et al. Low STAT3 expression sensitizes to toxic effects of beta-adrenergic receptor stimulation in peripartum cardiomyopathy. Eur. Heart J. 38, 349\u2013361 (2016).","journal-title":"Eur. Heart J."},{"key":"BFncomms14656_CR46","doi-asserted-by":"publisher","first-page":"3402","DOI":"10.4049\/jimmunol.168.7.3402","volume":"168","author":"R Lang","year":"2002","unstructured":"Lang, R., Rutschman, R. L., Greaves, D. R. & Murray, P. J. Autocrine deactivation of macrophages in transgenic mice constitutively overexpressing IL-10 under control of the human CD68 promoter. J. Immunol. 168, 3402\u20133411 (2002).","journal-title":"J. Immunol."},{"key":"BFncomms14656_CR47","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1097\/00019501-200502000-00008","volume":"16","author":"D Kumar","year":"2005","unstructured":"Kumar, D. et al. Distinct mouse coronary anatomy and myocardial infarction consequent to ligation. Coron. Artery Dis. 16, 41\u201344 (2005).","journal-title":"Coron. Artery Dis."},{"key":"BFncomms14656_CR48","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1161\/01.CIR.99.13.1685","volume":"99","author":"XL Ma","year":"1999","unstructured":"Ma, X. L. et al. Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion. Circulation 99, 1685\u20131691 (1999).","journal-title":"Circulation"},{"key":"BFncomms14656_CR49","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1038\/labinvest.3700322","volume":"85","author":"K Matsushita","year":"2005","unstructured":"Matsushita, K. et al. Interleukin-6\/soluble interleukin-6 receptor complex reduces infarct size via inhibiting myocardial apoptosis. Lab. Invest. 85, 1210\u20131223 (2005).","journal-title":"Lab. Invest."},{"key":"BFncomms14656_CR50","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1093\/eurheartj\/ehr131","volume":"34","author":"H Liang","year":"2013","unstructured":"Liang, H. et al. Increased expression of pigment epithelium-derived factor in aged mesenchymal stem cells impairs their therapeutic efficacy for attenuating myocardial infarction injury. Eur. Heart J. 34, 1681\u20131690 (2013).","journal-title":"Eur. Heart J."},{"key":"BFncomms14656_CR51","doi-asserted-by":"publisher","first-page":"3072","DOI":"10.1038\/srep03072","volume":"3","author":"S Horie","year":"2013","unstructured":"Horie, S. et al. CD200R signaling inhibits pro-angiogenic gene expression by macrophages and suppresses choroidal neovascularization. Sci. Rep. 3, 3072 (2013).","journal-title":"Sci. Rep."},{"key":"BFncomms14656_CR52","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1016\/j.jaci.2014.04.035","volume":"134","author":"M Shi","year":"2014","unstructured":"Shi, M. et al. Myeloid-derived suppressor cell function is diminished in aspirin-triggered allergic airway hyperresponsiveness in mice. J. Allergy Clin. Immunol. 134, 1163\u20131174 e1116 (2014).","journal-title":"J. Allergy Clin. Immunol."},{"key":"BFncomms14656_CR53","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.yjmcc.2013.04.023","volume":"62","author":"X Yan","year":"2013","unstructured":"Yan, X. et al. Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction. J. Mol. Cell. Cardiol. 62, 24\u201335 (2013).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"BFncomms14656_CR54","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1161\/CIRCULATIONAHA.106.632430","volume":"114","author":"S Hannenhalli","year":"2006","unstructured":"Hannenhalli, S. et al. Transcriptional genomics associates FOX transcription factors with human heart failure. Circulation 114, 1269\u20131276 (2006).","journal-title":"Circulation"},{"key":"BFncomms14656_CR55","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1038\/ncb2096","volume":"12","author":"MG Roukens","year":"2010","unstructured":"Roukens, M. G. et al. Control of endothelial sprouting by a Tel-CtBP complex. Nat. Cell Biol. 12, 933\u2013942 (2010).","journal-title":"Nat. Cell Biol."},{"key":"BFncomms14656_CR56","doi-asserted-by":"publisher","first-page":"5456","DOI":"10.1073\/pnas.070036297","volume":"97","author":"KM Kurrelmeyer","year":"2000","unstructured":"Kurrelmeyer, K. M. et al. Endogenous tumor necrosis factor protects the adult cardiac myocyte against ischemic-induced apoptosis in a murine model of acute myocardial infarction. Proc. Natl Acad. Sci. USA 97, 5456\u20135461 (2000).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms14656_CR57","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1182\/blood-2003-07-2624","volume":"104","author":"D Abdel-Latif","year":"2004","unstructured":"Abdel-Latif, D. et al. Rac2 is critical for neutrophil primary granule exocytosis. Blood 104, 832\u2013839 (2004).","journal-title":"Blood"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms14656.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms14656","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms14656.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:32Z","timestamp":1671753632000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms14656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,3]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,4,28]]}},"alternative-id":["BFncomms14656"],"URL":"https:\/\/doi.org\/10.1038\/ncomms14656","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,3]]},"assertion":[{"value":"19 August 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14656"}}