{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:27:21Z","timestamp":1792895241359,"version":"4.5.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T00:00:00Z","timestamp":1531440000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T00:00:00Z","timestamp":1531440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1123\/A2"],"award-info":[{"award-number":["SFB1123\/A2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1123\/A2"],"award-info":[{"award-number":["SFB1123\/A2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["016.126.358"],"award-info":[{"award-number":["016.126.358"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009425","name":"Landsteiner Foundation for Blood Transfusion Research","doi-asserted-by":"publisher","award":["1638"],"award-info":[{"award-number":["1638"]}],"id":[{"id":"10.13039\/100009425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"EC | European Research Council","doi-asserted-by":"publisher","award":["249929"],"award-info":[{"award-number":["249929"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Myocardial infarction (MI) is a major cause of death in Western countries and finding new strategies for its prevention and treatment is thus of high priority. In a previous study, we have demonstrated a pathophysiologic relevance for the heterophilic interaction of CCL5 and CXCL4 in the progression of atherosclerosis. A specifically designed compound (MKEY) to block this CCL5-CXCR4 interaction is investigated as a potential therapeutic in a model of myocardial ischemia\/reperfusion (I\/R) damage. 8 week-old male C57BL\/6 mice were intravenously treated with MKEY or scrambled control (sMKEY) from 1 day before, until up to 7 days after I\/R. By using echocardiography and intraventricular pressure measurements, MKEY treatment resulted in a significant decrease in infarction size and preserved heart function as compared to sMKEY-treated animals. Moreover, MKEY treatment significantly reduced the inflammatory reaction following I\/R, as revealed by specific staining for neutrophils and monocyte\/macrophages. Interestingly, MKEY treatment led to a significant reduction of citrullinated histone 3 in the infarcted tissue, showing that MKEY can prevent neutrophil extracellular trap formation <jats:italic>in vivo<\/jats:italic>. Disrupting chemokine heterodimers during myocardial I\/R might have clinical benefits, preserving the therapeutic benefit of blocking specific chemokines, and in addition, reducing the inflammatory side effects maintaining normal immune defence.<\/jats:p>","DOI":"10.1038\/s41598-018-29026-0","type":"journal-article","created":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T11:11:55Z","timestamp":1531134715000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Blocking CCL5-CXCL4 heteromerization preserves heart function after myocardial infarction by attenuating leukocyte recruitment and NETosis"],"prefix":"10.1038","volume":"8","author":[{"given":"Tanja","family":"Vajen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9955-9730","authenticated-orcid":false,"given":"Rory R.","family":"Koenen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Werner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mareike","family":"Staudt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia","family":"Projahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelina","family":"Curaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolga Taha","family":"S\u00f6nmez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakine","family":"Simsekyilmaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Schumacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"M\u00f6llmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman M.","family":"Hackeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp von","family":"Hundelshausen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1253-3272","authenticated-orcid":false,"given":"Elisa A.","family":"Liehn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,7,13]]},"reference":[{"key":"29026_CR1","doi-asserted-by":"publisher","first-page":"4226","DOI":"10.1096\/fj.201700109R","volume":"31","author":"B Tourki","year":"2017","unstructured":"Tourki, B. & Halade, G. Leukocyte diversity in resolving and nonresolving mechanisms of cardiac remodeling. FASEB J 31, 4226\u20134239, https:\/\/doi.org\/10.1096\/fj.201700109R (2017).","journal-title":"FASEB J"},{"key":"29026_CR2","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1093\/eurheartj\/ehw002","volume":"38","author":"M Horckmans","year":"2017","unstructured":"Horckmans, M. et al. Neutrophils orchestrate post-myocardial infarction healing by polarizing macrophages towards a reparative phenotype. Eur Heart J 38, 187\u2013197, https:\/\/doi.org\/10.1093\/eurheartj\/ehw002 (2017).","journal-title":"Eur Heart J"},{"key":"29026_CR3","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1016\/j.jacc.2011.08.034","volume":"58","author":"EA Liehn","year":"2011","unstructured":"Liehn, E. A., Postea, O., Curaj, A. & Marx, N. Repair after myocardial infarction, between fantasy and reality: the role of chemokines. J Am Coll Cardiol 58, 2357\u20132362, https:\/\/doi.org\/10.1016\/j.jacc.2011.08.034 (2011).","journal-title":"J Am Coll Cardiol"},{"key":"29026_CR4","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1126\/science.1230719","volume":"339","author":"FK Swirski","year":"2013","unstructured":"Swirski, F. K. & Nahrendorf, M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science 339, 161\u2013166, https:\/\/doi.org\/10.1126\/science.1230719 (2013).","journal-title":"Science"},{"key":"29026_CR5","doi-asserted-by":"publisher","first-page":"e41","DOI":"10.15190\/d.2015.33","volume":"3","author":"NG Frangogiannis","year":"2015","unstructured":"Frangogiannis, N. G. Interleukin-1 in cardiac injury, repair, and remodeling: pathophysiologic and translational concepts. Discoveries 3, e41, https:\/\/doi.org\/10.15190\/d.2015.33 (2015).","journal-title":"Discoveries"},{"key":"29026_CR6","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1124\/pr.113.008300","volume":"66","author":"P Ferdinandy","year":"2014","unstructured":"Ferdinandy, P., Hausenloy, D. J., Heusch, G., Baxter, G. F. & Schulz, R. Interaction of risk factors, comorbidities, and comedications with ischemia\/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Pharmacol Rev 66, 1142\u20131174, https:\/\/doi.org\/10.1124\/pr.113.008300 (2014).","journal-title":"Pharmacol Rev"},{"key":"29026_CR7","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1093\/cvr\/cvu225","volume":"104","author":"S Lecour","year":"2014","unstructured":"Lecour, S. et al. ESC working group cellular biology of the heart: position paper: improving the preclinical assessment of novel cardioprotective therapies. Cardiovasc Res 104, 399\u2013411, https:\/\/doi.org\/10.1093\/cvr\/cvu225 (2014).","journal-title":"Cardiovasc Res"},{"key":"29026_CR8","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1002\/emmm.201100183","volume":"3","author":"RR Koenen","year":"2011","unstructured":"Koenen, R. R. & Weber, C. Chemokines: established and novel targets in atherosclerosis. EMBO Mol Med 3, 713\u2013725, https:\/\/doi.org\/10.1002\/emmm.201100183 (2011).","journal-title":"EMBO Mol Med"},{"key":"29026_CR9","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1161\/01.RES.0000163017.13772.3a","volume":"96","author":"O Dewald","year":"2005","unstructured":"Dewald, O. et al. CCL2\/Monocyte Chemoattractant Protein-1 regulates inflammatory responses critical to healing myocardial infarcts. Circulation Research 96, 881\u2013889, https:\/\/doi.org\/10.1161\/01.RES.0000163017.13772.3a (2005).","journal-title":"Circulation Research"},{"key":"29026_CR10","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1111\/j.1582-4934.2007.00194.x","volume":"12","author":"EA Liehn","year":"2008","unstructured":"Liehn, E. A. et al. Ccr1 deficiency reduces inflammatory remodelling and preserves left ventricular function after myocardial infarction. J Cell Mol Med 12, 496\u2013506, https:\/\/doi.org\/10.1111\/j.1582-4934.2007.00194.x (2008).","journal-title":"J Cell Mol Med"},{"key":"29026_CR11","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1016\/j.jacc.2010.04.066","volume":"56","author":"EA Liehn","year":"2010","unstructured":"Liehn, E. A. et al. A new monocyte chemotactic protein-1\/chemokine CC motif ligand-2 competitor limiting neointima formation and myocardial ischemia\/reperfusion injury in mice. J Am Coll Cardiol 56, 1847\u20131857, https:\/\/doi.org\/10.1016\/j.jacc.2010.04.066 (2010).","journal-title":"J Am Coll Cardiol"},{"key":"29026_CR12","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1093\/eurheartj\/ehr127","volume":"33","author":"F Montecucco","year":"2012","unstructured":"Montecucco, F. et al. CC chemokine CCL5 plays a central role impacting infarct size and post-infarction heart failure in mice. Eur Heart J 33, 1964\u20131974, https:\/\/doi.org\/10.1093\/eurheartj\/ehr127 (2012).","journal-title":"Eur Heart J"},{"key":"29026_CR13","doi-asserted-by":"publisher","first-page":"317ra196","DOI":"10.1126\/scitranslmed.aad5330","volume":"7","author":"JE Alard","year":"2015","unstructured":"Alard, J. E. et al. Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5. Sci Transl Med 7, 317ra196, https:\/\/doi.org\/10.1126\/scitranslmed.aad5330 (2015).","journal-title":"Sci Transl Med"},{"key":"29026_CR14","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1111\/j.0300-9475.2004.01399.x","volume":"59","author":"LN Sorensen","year":"2004","unstructured":"Sorensen, L. N. & Paludan, S. R. Blocking CC chemokine receptor (CCR) 1 and CCR5 during herpes simplex virus type 2 infection in vivo impairs host defence and perturbs the cytokine response. Scand J Immunol 59, 321\u2013333 (2004).","journal-title":"Scand J Immunol"},{"key":"29026_CR15","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1084\/jem.20051970","volume":"203","author":"WG Glass","year":"2006","unstructured":"Glass, W. G. et al. CCR5 deficiency increases risk of symptomatic West Nile virus infection. J Exp Med 203, 35\u201340 (2006).","journal-title":"J Exp Med"},{"key":"29026_CR16","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/ni1309","volume":"7","author":"NV Serbina","year":"2006","unstructured":"Serbina, N. V. & Pamer, E. G. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 7, 311\u2013317 (2006).","journal-title":"Nat Immunol"},{"key":"29026_CR17","doi-asserted-by":"publisher","first-page":"5658","DOI":"10.4049\/jimmunol.170.11.5658","volume":"170","author":"HJ Anders","year":"2003","unstructured":"Anders, H. J. et al. CC chemokine ligand 5\/RANTES chemokine antagonists aggravate glomerulonephritis despite reduction of glomerular leukocyte infiltration. J Immunol 170, 5658\u20135666 (2003).","journal-title":"J Immunol"},{"key":"29026_CR18","doi-asserted-by":"crossref","first-page":"4020","DOI":"10.1182\/blood.V94.12.4020","volume":"94","author":"F Petersen","year":"1999","unstructured":"Petersen, F., Bock, L., Flad, H. D. & Brandt, E. Platelet factor 4-induced neutrophil-endothelial cell interaction: involvement of mechanisms and functional consequences different from those elicited by interleukin-8. Blood 94, 4020\u20134028 (1999).","journal-title":"Blood"},{"key":"29026_CR19","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1182\/blood-2004-06-2475","volume":"105","author":"P von Hundelshausen","year":"2005","unstructured":"von Hundelshausen, P. et al. Heterophilic interactions of platelet factor 4 and RANTES promote monocyte arrest on endothelium. Blood 105, 924\u2013930, https:\/\/doi.org\/10.1182\/blood-2004-06-2475 (2005).","journal-title":"Blood"},{"key":"29026_CR20","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nm.1898","volume":"15","author":"RR Koenen","year":"2009","unstructured":"Koenen, R. R. et al. Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice. Nat Med 15, 97\u2013103, https:\/\/doi.org\/10.1038\/nm.1898 (2009).","journal-title":"Nat Med"},{"key":"29026_CR21","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1164\/rccm.201108-1533OC","volume":"185","author":"J Grommes","year":"2012","unstructured":"Grommes, J. et al. Disruption of platelet-derived chemokine heteromers prevents neutrophil extravasation in acute lung injury. Am J Respir Crit Care Med 185, 628\u2013636, https:\/\/doi.org\/10.1164\/rccm.201108-1533OC (2012).","journal-title":"Am J Respir Crit Care Med"},{"key":"29026_CR22","doi-asserted-by":"publisher","unstructured":"von Hundelshausen, P. et al. Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation. Sci Transl Med 9, https:\/\/doi.org\/10.1126\/scitranslmed.aah6650 (2017).","DOI":"10.1126\/scitranslmed.aah6650"},{"key":"29026_CR23","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.1182\/blood-2013-07-516484","volume":"123","author":"J Rossaint","year":"2014","unstructured":"Rossaint, J. et al. Synchronized integrin engagement and chemokine activation is crucial in neutrophil extracellular trap-mediated sterile inflammation. Blood 123, 2573\u20132584, https:\/\/doi.org\/10.1182\/blood-2013-07-516484 (2014).","journal-title":"Blood"},{"key":"29026_CR24","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1161\/ATVBAHA.112.300329","volume":"33","author":"Y Iida","year":"2013","unstructured":"Iida, Y. et al. Peptide inhibitor of CXCL4-CCL5 heterodimer formation, MKEY, inhibits experimental aortic aneurysm initiation and progression. Arterioscler Thromb Vasc Biol 33, 718\u2013726, https:\/\/doi.org\/10.1161\/ATVBAHA.112.300329 (2013).","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"29026_CR25","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.yjmcc.2009.07.029","volume":"48","author":"V Braunersreuther","year":"2010","unstructured":"Braunersreuther, V. et al. Chemokine CCL5\/RANTES inhibition reduces myocardial reperfusion injury in atherosclerotic mice. Journal of Molecular and Cellular Cardiology 48, 789\u2013798, https:\/\/doi.org\/10.1016\/j.yjmcc.2009.07.029 (2010).","journal-title":"Journal of Molecular and Cellular Cardiology"},{"key":"29026_CR26","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1111\/jcmm.12225","volume":"18","author":"D Projahn","year":"2014","unstructured":"Projahn, D. et al. Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction. J Cell Mol Med 18, 790\u2013800, https:\/\/doi.org\/10.1111\/jcmm.12225 (2014).","journal-title":"J Cell Mol Med"},{"key":"29026_CR27","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1182\/blood-2013-07-514992","volume":"123","author":"AS Savchenko","year":"2014","unstructured":"Savchenko, A. S. et al. VWF-mediated leukocyte recruitment with chromatin decondensation by PAD4 increases myocardial ischemia\/reperfusion injury in mice. Blood 123, 141\u2013148, https:\/\/doi.org\/10.1182\/blood-2013-07-514992 (2014).","journal-title":"Blood"},{"key":"29026_CR28","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":"29026_CR29","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.immuni.2013.11.019","volume":"40","author":"S Epelman","year":"2014","unstructured":"Epelman, S. et al. Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity 40, 91\u2013104, https:\/\/doi.org\/10.1016\/j.immuni.2013.11.019 (2014).","journal-title":"Immunity"},{"key":"29026_CR30","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1172\/JCI28549","volume":"117","author":"F Tacke","year":"2007","unstructured":"Tacke, F. et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest 117, 185\u2013194 (2007).","journal-title":"J Clin Invest"},{"key":"29026_CR31","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1002\/emmm.201201717","volume":"5","author":"O Soehnlein","year":"2013","unstructured":"Soehnlein, O. et al. Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes. EMBO Mol Med 5, 471\u2013481, https:\/\/doi.org\/10.1002\/emmm.201201717 (2013).","journal-title":"EMBO Mol Med"},{"key":"29026_CR32","doi-asserted-by":"publisher","unstructured":"Fan, Y. et al. MKEY, a Peptide Inhibitor of CXCL4-CCL5 Heterodimer Formation, Protects Against Stroke in Mice. J Am Heart Assoc 5, https:\/\/doi.org\/10.1161\/JAHA.116.003615 (2016).","DOI":"10.1161\/JAHA.116.003615"},{"key":"29026_CR33","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1007\/s00395-012-0310-4","volume":"108","author":"I Kanzler","year":"2013","unstructured":"Kanzler, I. et al. Differential roles of angiogenic chemokines in endothelial progenitor cell-induced angiogenesis. Basic Res Cardiol 108, 310, https:\/\/doi.org\/10.1007\/s00395-012-0310-4 (2013).","journal-title":"Basic Res Cardiol"},{"key":"29026_CR34","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1016\/j.tips.2017.03.001","volume":"38","author":"Y Ma","year":"2017","unstructured":"Ma, Y., Iyer, R. P., Jung, M., Czubryt, M. P. & Lindsey, M. L. Cardiac Fibroblast Activation Post-Myocardial Infarction: Current Knowledge Gaps. Trends Pharmacol Sci 38, 448\u2013458, https:\/\/doi.org\/10.1016\/j.tips.2017.03.001 (2017).","journal-title":"Trends Pharmacol Sci"},{"key":"29026_CR35","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1160\/TH07-10-0628","volume":"99","author":"PE Westerweel","year":"2008","unstructured":"Westerweel, P. E., Rabelink, T. J., Rookmaaker, M. B., Grone, H. J. & Verhaar, M. C. RANTES is required for ischaemia-induced angiogenesis, which may hamper RANTES-targeted anti-atherosclerotic therapy. Thromb Haemost 99, 794\u2013795, https:\/\/doi.org\/10.1160\/TH07-10-0628 (2008).","journal-title":"Thromb Haemost"},{"key":"29026_CR36","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S1044-5323(02)00128-8","volume":"15","author":"AE Proudfoot","year":"2003","unstructured":"Proudfoot, A. E., Power, C. A., Rommel, C. & Wells, T. N. Strategies for chemokine antagonists as therapeutics. Semin Immunol 15, 57\u201365 (2003).","journal-title":"Semin Immunol"},{"key":"29026_CR37","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/nrd2734","volume":"8","author":"R Horuk","year":"2009","unstructured":"Horuk, R. Chemokine receptor antagonists: overcoming developmental hurdles. Nat Rev Drug Discov 8, 23\u201333 (2009).","journal-title":"Nat Rev Drug Discov"},{"key":"29026_CR38","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/nrd3048","volume":"9","author":"RR Koenen","year":"2010","unstructured":"Koenen, R. R. & Weber, C. Therapeutic targeting of chemokine interactions in atherosclerosis. Nat Rev Drug Discov 9, 141\u2013153, https:\/\/doi.org\/10.1038\/nrd3048 (2010).","journal-title":"Nat Rev Drug Discov"},{"key":"29026_CR39","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1161\/01.ATV.0000258789.21585.76","volume":"27","author":"E Cavusoglu","year":"2007","unstructured":"Cavusoglu, E. et al. Low plasma RANTES levels are an independent predictor of cardiac mortality in patients referred for coronary angiography. Arterioscler Thromb Vasc Biol 27, 929\u2013935 (2007).","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"29026_CR40","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1161\/CIRCULATIONAHA.107.706986","volume":"116","author":"AO Kraaijeveld","year":"2007","unstructured":"Kraaijeveld, A. O. et al. CC chemokine ligand-5 (CCL5\/RANTES) and CC chemokine ligand-18 (CCL18\/PARC) are specific markers of refractory unstable angina pectoris and are transiently raised during severe ischemic symptoms. Circulation 116, 1931\u20131941 (2007).","journal-title":"Circulation"},{"key":"29026_CR41","doi-asserted-by":"publisher","first-page":"37","DOI":"10.2174\/138920112798868557","volume":"13","author":"I Kanzler","year":"2012","unstructured":"Kanzler, I., Liehn, E. A., Koenen, R. R. & Weber, C. Anti-inflammatory therapeutic approaches to reduce acute atherosclerotic complications. Curr Pharm Biotechnol 13, 37\u201345 (2012).","journal-title":"Curr Pharm Biotechnol"},{"key":"29026_CR42","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1161\/01.ATV.0000253886.44609.ae","volume":"27","author":"V Braunersreuther","year":"2007","unstructured":"Braunersreuther, V. et al. Ccr5 but not Ccr1 deficiency reduces development of diet-induced atherosclerosis in mice. Arterioscler Thromb Vasc Biol 27, 373\u2013379 (2007).","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"29026_CR43","doi-asserted-by":"publisher","first-page":"4240","DOI":"10.1182\/blood-2005-09-3922","volume":"107","author":"A Zernecke","year":"2006","unstructured":"Zernecke, A. et al. Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10. Blood 107, 4240\u20134243 (2006).","journal-title":"Blood"},{"key":"29026_CR44","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.2353\/ajpath.2010.090759","volume":"176","author":"M Dobaczewski","year":"2010","unstructured":"Dobaczewski, M., Xia, Y., Bujak, M., Gonzalez-Quesada, C. & Frangogiannis, N. G. CCR5 signaling suppresses inflammation and reduces adverse remodeling of the infarcted heart, mediating recruitment of regulatory T cells. Am J Pathol 176, 2177\u20132187, https:\/\/doi.org\/10.2353\/ajpath.2010.090759 (2010).","journal-title":"Am J Pathol"},{"key":"29026_CR45","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1161\/ATVBAHA.108.165423","volume":"28","author":"V Braunersreuther","year":"2008","unstructured":"Braunersreuther, V. et al. A Novel RANTES Antagonist Prevents Progression of Established Atherosclerotic Lesions in Mice. Arterioscler Thromb Vasc Biol 28, 1090\u20131096 (2008).","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"29026_CR46","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1161\/01.RES.0000109793.17591.4E","volume":"94","author":"NR Veillard","year":"2004","unstructured":"Veillard, N. R. et al. Antagonism of RANTES receptors reduces atherosclerotic plaque formation in mice. Circ Res 94, 253\u2013261 (2004).","journal-title":"Circ Res"},{"key":"29026_CR47","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1006\/clim.2001.5178","volume":"102","author":"Y Makino","year":"2002","unstructured":"Makino, Y. et al. Impaired T cell function in RANTES-deficient mice. Clin Immunol 102, 302\u2013309 (2002).","journal-title":"Clin Immunol"},{"key":"29026_CR48","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1038\/nm1303","volume":"11","author":"JW Tyner","year":"2005","unstructured":"Tyner, J. W. et al. CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection. Nat Med 11, 1180\u20131187 (2005).","journal-title":"Nat Med"},{"key":"29026_CR49","doi-asserted-by":"publisher","first-page":"4584","DOI":"10.1073\/pnas.78.7.4584","volume":"78","author":"TF Deuel","year":"1981","unstructured":"Deuel, T. F. et al. Platelet factor 4 is chemotactic for neutrophils and monocytes. Proc Natl Acad Sci USA 78, 4584\u20134587 (1981).","journal-title":"Proc Natl Acad Sci USA"},{"key":"29026_CR50","first-page":"506","volume":"11","author":"F Petersen","year":"2000","unstructured":"Petersen, F. et al. Is platelet factor-4 a chemokine? Eur Cytokine Netw 11, 506\u2013507 (2000).","journal-title":"Eur Cytokine Netw"},{"key":"29026_CR51","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1160\/TH13-04-0341","volume":"110","author":"E Karshovska","year":"2013","unstructured":"Karshovska, E., Weber, C. & von Hundelshausen, P. Platelet chemokines in health and disease. Thromb Haemost 110, 894\u2013902, https:\/\/doi.org\/10.1160\/TH13-04-0341 (2013).","journal-title":"Thromb Haemost"},{"key":"29026_CR52","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1160\/TH07-04-0271","volume":"98","author":"BS Sachais","year":"2007","unstructured":"Sachais, B. S. et al. Elimination of platelet factor 4 (PF4) from platelets reduces atherosclerosis in C57Bl\/6 and apoE\u2212\/\u2212 mice. Thromb Haemost 98, 1108\u20131113 (2007).","journal-title":"Thromb Haemost"},{"key":"29026_CR53","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1161\/ATVBAHA.109.187716","volume":"29","author":"H Wang","year":"2009","unstructured":"Wang, H. et al. Core2 1-6-N-glucosaminyltransferase-I deficiency protects injured arteries from neointima formation in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 29, 1053\u20131059, https:\/\/doi.org\/10.1161\/ATVBAHA.109.187716 (2009).","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"29026_CR54","doi-asserted-by":"publisher","first-page":"4417","DOI":"10.1182\/blood-2012-09-454710","volume":"121","author":"G Shi","year":"2013","unstructured":"Shi, G. et al. Platelet factor 4 mediates vascular smooth muscle cell injury responses. Blood 121, 4417\u20134427, https:\/\/doi.org\/10.1182\/blood-2012-09-454710 (2013).","journal-title":"Blood"},{"key":"29026_CR55","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1160\/th14-02-0139","volume":"112","author":"X Blanchet","year":"2014","unstructured":"Blanchet, X. et al. Inflammatory role and prognostic value of platelet chemokines in acute coronary syndrome. Thromb Haemost 112, 1277\u20131287, https:\/\/doi.org\/10.1160\/TH14-02-0139 (2014).","journal-title":"Thromb Haemost"},{"key":"29026_CR56","first-page":"67","volume":"32","author":"G Caimi","year":"2005","unstructured":"Caimi, G. et al. Plasma markers of platelet and polymorphonuclear leukocyte activation in young adults with acute myocardial infarction. Clin Hemorheol Microcirc 32, 67\u201374 (2005).","journal-title":"Clin Hemorheol Microcirc"},{"key":"29026_CR57","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1160\/TH13-05-0420","volume":"110","author":"BK Kramp","year":"2013","unstructured":"Kramp, B. K. et al. Exchange of extracellular domains of CCR1 and CCR5 reveals confined functions in CCL5-mediated cell recruitment. Thromb Haemost 110, 795\u2013806, https:\/\/doi.org\/10.1160\/TH13-05-0420 (2013).","journal-title":"Thromb Haemost"},{"key":"29026_CR58","doi-asserted-by":"publisher","first-page":"e000874","DOI":"10.1161\/JAHA.114.000874","volume":"3","author":"KM Kelly","year":"2014","unstructured":"Kelly, K. M. et al. CCR5 inhibition prevents cardiac dysfunction in the SIV\/macaque model of HIV. J Am Heart Assoc 3, e000874, https:\/\/doi.org\/10.1161\/JAHA.114.000874 (2014).","journal-title":"J Am Heart Assoc"},{"key":"29026_CR59","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1161\/01.CIR.98.13.1322","volume":"98","author":"AM Lefer","year":"1998","unstructured":"Lefer, A. M., Campbell, B., Scalia, R. & Lefer, D. J. Synergism between platelets and neutrophils in provoking cardiac dysfunction after ischemia and reperfusion: role of selectins. Circulation 98, 1322\u20131328 (1998).","journal-title":"Circulation"},{"key":"29026_CR60","doi-asserted-by":"publisher","first-page":"2226","DOI":"10.1161\/01.ATV.20.10.2226","volume":"20","author":"C Kupatt","year":"2000","unstructured":"Kupatt, C. et al. c7E3Fab reduces postischemic leukocyte-thrombocyte interaction mediated by fibrinogen. Implications for myocardial reperfusion injury. Arterioscler Thromb Vasc Biol 20, 2226\u20132232 (2000).","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"29026_CR61","doi-asserted-by":"publisher","unstructured":"Curaj, A., Simsekyilmaz, S., Staudt, M. & Liehn, E. Minimal invasive surgical procedure of inducing myocardial infarction in mice. J. Vis. Exp., e52197, https:\/\/doi.org\/10.3791\/52197 (2015).","DOI":"10.3791\/52197"},{"key":"29026_CR62","doi-asserted-by":"publisher","unstructured":"Brinkmann, V., Laube, B., Abu Abed, U., Goosmann, C. & Zychlinsky, A. Neutrophil extracellular traps: how to generate and visualize them. J. Vis. Exp., https:\/\/doi.org\/10.3791\/1724 (2010).","DOI":"10.3791\/1724"},{"key":"29026_CR63","doi-asserted-by":"publisher","first-page":"e19","DOI":"10.15190\/d.2014.11","volume":"2","author":"M Saffarzadeh","year":"2014","unstructured":"Saffarzadeh, M. et al. Characterization of rapid neutrophil extracellular trap formation and its cooperation with phagocytosis in human neutrophils. Discoveries 2, e19, https:\/\/doi.org\/10.15190\/d.2014.11 (2014).","journal-title":"Discoveries"},{"key":"29026_CR64","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1046\/j.1365-2141.1998.00844.x","volume":"102","author":"MA Feijge","year":"1998","unstructured":"Feijge, M. A. et al. Inter-individual variability in Ca2+ signalling in platelets from healthy volunteers: effects of aspirin and relationship with expression of endomembrane Ca2+ -ATPases. Br J Haematol 102, 850\u2013859 (1998).","journal-title":"Br J Haematol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-29026-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-29026-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-29026-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T07:27:28Z","timestamp":1671607648000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-29026-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,13]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["29026"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-29026-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,13]]},"assertion":[{"value":"21 November 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"These authors declare competing financial interests: Christian Weber, Philipp von Hundelshausen, and Rory R. Koenen are shareholders of Carolus Therapeutics Inc., San Diego, CA, now Anemot Therapeutics Inc, Raleigh-Durham, NC. All other authors have nothing to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"10647"}}