{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T17:12:15Z","timestamp":1787073135043,"version":"build-2736575974"},"reference-count":69,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,16]],"date-time":"2023-12-16T00:00:00Z","timestamp":1702684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several studies have demonstrated that, beyond their antithrombotic effects, P2Y12 receptor inhibitors may provide additional off-target effects through different mechanisms. These effects range from the preservation of endothelial barrier function to the modulation of inflammation or stabilization of atherosclerotic plaques, with an impact on different cell types, including endothelial and immune cells. Many P2Y12 inhibitors have been developed, from ticlopidine, the first thienopyridine, to the more potent non-thienopyridine derivatives such as ticagrelor which may promote cardioprotective effects following myocardial infarction (MI) by inhibiting adenosine reuptake through sodium-independent equilibrative nucleoside transporter 1 (ENT1). Adenosine may affect different molecular pathways involved in cardiac fibrosis, such as the Wnt (wingless-type)\/beta (\u03b2)-catenin signaling. An early pro-fibrotic response of the epicardium and activation of cardiac fibroblasts with the involvement of Wnt1 (wingless-type family member 1)\/\u03b2-catenin, are critically required for preserving cardiac function after acute ischemic cardiac injury. This review discusses molecular signaling pathways involved in cardiac fibrosis post MI, focusing on the Wnt\/\u03b2-catenin pathway, and the off-target effect of P2Y12 receptor inhibition. A potential role of ticagrelor was speculated in the early modulation of cardiac fibrosis, thanks to its off-target effect.<\/jats:p>","DOI":"10.3390\/ijms242417546","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T03:59:24Z","timestamp":1702871964000},"page":"17546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Off-Target Effects of P2Y12 Receptor Inhibitors: Focus on Early Myocardial Fibrosis Modulation"],"prefix":"10.3390","volume":"24","author":[{"given":"Francesca","family":"Lofrumento","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Policlinic \u201cG. Martino\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Irrera","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Policlinic \u201cG. Martino\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3185-9240","authenticated-orcid":false,"given":"Roberto","family":"Licordari","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Policlinic \u201cG. Martino\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8587-2382","authenticated-orcid":false,"given":"Silvia","family":"Perfetti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Policlinic \u201cG. Martino\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Nasso","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Policlinic \u201cG. Martino\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Liotta","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Policlinic \u201cG. Martino\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Isgr\u00f2","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Policlinic \u201cG. Martino\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Garcia-Ruiz","sequence":"additional","affiliation":[{"name":"Cardiology Department, GIOMI Hospital, 98165 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Squadrito","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Policlinic \u201cG. Martino\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scipione","family":"Carerj","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Policlinic \u201cG. Martino\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Di Bella","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Policlinic \u201cG. Martino\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Micari","sequence":"additional","affiliation":[{"name":"BIOMORF Department, Policlinic \u201cG. Martino\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3097-2834","authenticated-orcid":false,"given":"Francesco","family":"Costa","sequence":"additional","affiliation":[{"name":"BIOMORF Department, Policlinic \u201cG. Martino\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1093\/eurheartj\/ehab892","article-title":"European Society of Cardiology: Cardiovascular disease statistics 2021","volume":"43","author":"Timmis","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1161\/CIRCRESAHA.113.300268","article-title":"Epidemiology of Heart Failure","volume":"113","author":"Roger","year":"2013","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s00441-016-2431-9","article-title":"Cardiac fibrosis in myocardial infarction\u2014From repair and remodeling to regeneration","volume":"365","author":"Talman","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1080\/13543784.2021.1868432","article-title":"Cardiac fibrosis: Emerging agents in preclinical and clinical development","volume":"30","author":"Spoladore","year":"2021","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1093\/eurheartj\/ehad191","article-title":"2023 ESC Guidelines for the management of acute coronary syndromes","volume":"44","author":"Byrne","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1093\/eurheartj\/ehp296","article-title":"P2Y12 inhibitors: Differences in properties and mechanisms of action and potential consequences for clinical use","volume":"30","author":"Wallentin","year":"2009","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/eurheartj\/ehx419","article-title":"2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS","volume":"39","author":"Valgimigli","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1160\/TH13-11-0915","article-title":"Overview of pleiotropic effects of platelet P2Y12 receptor inhibitors","volume":"112","author":"Adamski","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1111\/bph.13429","article-title":"Effects of P2Y12 receptor antagonists beyond platelet inhibition\u2013comparison of ticagrelor with thienopyridines","volume":"173","author":"Nylander","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e12175","DOI":"10.14814\/phy2.12175","article-title":"cAMP controls the restoration of endothelial barrier function after thrombin-induced hyperpermeability via Rac1 activation","volume":"2","author":"Aslam","year":"2014","journal-title":"Physiol. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1016\/j.jacc.2014.03.031","article-title":"Adenosine-Mediated Effects of Ticagrelor","volume":"63","author":"Cattaneo","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41392-021-00553-z","article-title":"From purines to purinergic signalling: Molecular functions and human diseases","volume":"6","author":"Huang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mansour, A., Bachelot-Loza, C., Nesseler, N., Gaussem, P., and Gouin-Thibault, I. (2020). P2Y12 Inhibition beyond Thrombosis: Effects on Inflammation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041391"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Procopio, M.C., Lauro, R., Nasso, C., Carerj, S., Squadrito, F., Bitto, A., Di Bella, G., Micari, A., Irrera, N., and Costa, F. (2021). Role of Adenosine and Purinergic Receptors in Myocardial Infarction: Focus on Different Signal Transduction Pathways. Biomedicines, 9.","DOI":"10.3390\/biomedicines9020204"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.drudis.2018.09.021","article-title":"Antithrombotic P2Y12 receptor antagonists: Recent developments in drug discovery","volume":"24","author":"Baqi","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1124\/dmd.110.032250","article-title":"Absorption, Distribution, Metabolism, and Excretion of Ticagrelor in Healthy Subjects","volume":"38","author":"Teng","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1056\/NEJMoa0904327","article-title":"Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes","volume":"361","author":"Wallentin","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1056\/NEJMoa0706482","article-title":"Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes","volume":"357","author":"Wiviott","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1093\/eurheartj\/ehv104","article-title":"Bleeding and stent thrombosis on P2Y12-inhibitors: Collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention","volume":"36","author":"Aradi","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1161\/CIRCOUTCOMES.111.964395","article-title":"Ticagrelor Versus Clopidogrel in Elderly Patients with Acute Coronary Syndromes","volume":"5","author":"Husted","year":"2012","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1161\/ATVBAHA.115.303395","article-title":"Purinergic Receptors in Thrombosis and Inflammation","volume":"35","author":"Hechler","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1160\/TH14-12-1067","article-title":"The role of platelets in inflammation","volume":"114","author":"Thomas","year":"2015","journal-title":"Thromb. Haemost."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1113\/jphysiol.2012.237834","article-title":"Hypoxia-reoxygenation-induced endothelial barrier failure: Role of RhoA, Rac1 and myosin light chain kinase","volume":"591","author":"Aslam","year":"2013","journal-title":"J. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"H853","DOI":"10.1152\/ajpheart.00862.2013","article-title":"Involvement of P2Y12 receptor in vascular smooth muscle inflammatory changes via MCP-1 upregulation and monocyte adhesion","volume":"308","author":"Satonaka","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1160\/TH12-08-0547","article-title":"Why does ticagrelor induce dyspnea?","volume":"108","author":"Cattaneo","year":"2012","journal-title":"Thromb. Haemost."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1177\/1074248411410883","article-title":"Ticagrelor Inhibits Adenosine Uptake In Vitro and Enhances Adenosine-Mediated Hyperemia Responses in a Canine Model","volume":"17","author":"Sidaway","year":"2012","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1161\/ATVBAHA.114.304002","article-title":"Chronic Treatment with Ticagrelor Limits Myocardial Infarct Size","volume":"34","author":"Nanhwan","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1161\/CIRCULATIONAHA.116.024710","article-title":"The Dogged Search for Cryptic Effects of Ticagrelor","volume":"134","author":"Gurbel","year":"2016","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1161\/CIRCULATIONAHA.116.024014","article-title":"Protective Effects of Ticagrelor on Myocardial Injury After Infarction","volume":"134","author":"Vilahur","year":"2016","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1161\/CIRCINTERVENTIONS.113.000293","article-title":"Differential Effect of Ticagrelor Versus Prasugrel on Coronary Blood Flow Velocity in Patients with Non\u2013ST-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention","volume":"6","author":"Alexopoulos","year":"2013","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.jacc.2013.09.067","article-title":"Ticagrelor Increases Adenosine Plasma Concentration in Patients with an Acute Coronary Syndrome","volume":"63","author":"Bonello","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.jacc.2012.11.032","article-title":"Ticagrelor Enhances Adenosine-Induced Coronary Vasodilatory Responses in Humans","volume":"61","author":"Wittfeldt","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1016\/j.jcin.2017.05.064","article-title":"Comparison of Ticagrelor Versus Prasugrel for Inflammation, Vascular Function, and Circulating Endothelial Progenitor Cells in Diabetic Patients with Non\u2013ST-Segment Elevation Acute Coronary Syndrome Requiring Coronary Stenting","volume":"10","author":"Jeong","year":"2017","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1016\/j.jcin.2018.04.022","article-title":"Effects of Ticagrelor, Prasugrel, or Clopidogrel on Endothelial Function and Other Vascular Biomarkers","volume":"11","author":"Ariotti","year":"2018","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"517","DOI":"10.3109\/09537104.2013.842965","article-title":"Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study","volume":"25","author":"Storey","year":"2014","journal-title":"Platelets"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.vph.2015.02.006","article-title":"Ticagrelor potentiates adenosine-induced stimulation of neutrophil chemotaxis and phagocytosis","volume":"71","author":"Alsharif","year":"2015","journal-title":"Vasc. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1056\/NEJMoa1500857","article-title":"Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction","volume":"372","author":"Bonaca","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.jacbts.2018.05.005","article-title":"Ticagrelor Reduces Thromboinflammatory Markers in Patients with Pneumonia","volume":"3","author":"Sexton","year":"2018","journal-title":"JACC Basic. Transl. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1001\/jamacardio.2019.1189","article-title":"Antibacterial Activity of Ticagrelor in Conventional Antiplatelet Dosages Against Antibiotic-Resistant Gram-Positive Bacteria","volume":"4","author":"Lancellotti","year":"2019","journal-title":"JAMA Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1177\/1074248413511693","article-title":"Characterization of the Adenosine Pharmacology of Ticagrelor Reveals Therapeutically Relevant Inhibition of Equilibrative Nucleoside Transporter 1","volume":"19","author":"Armstrong","year":"2014","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1161\/01.CIR.80.5.1388","article-title":"Intracoronary adenosine administered after reperfusion limits vascular injury after prolonged ischemia in the canine model","volume":"80","author":"Babbitt","year":"1989","journal-title":"Circulation"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1161\/01.CIR.85.2.659","article-title":"Intravenous pretreatment with A1-selective adenosine analogues protects the heart against infarction","volume":"85","author":"Thornton","year":"1992","journal-title":"Circulation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1016\/j.jcin.2017.06.014","article-title":"More Evidence for Non-P2Y12-Mediated Effects of Ticagrelor","volume":"10","author":"Tantry","year":"2017","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e935664","DOI":"10.12659\/MSM.935664","article-title":"A Review of the Role of the Antiplatelet Drug Ticagrelor in the Management of Acute Coronary Syndrome, Acute Thrombotic Disease, and Other Diseases","volume":"28","author":"Tao","year":"2022","journal-title":"Med. Sci. Monit."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"553","DOI":"10.2147\/DDDT.S113289","article-title":"Adenosine A2A receptor agonist prevents cardiac remodeling and dysfunction in spontaneously hypertensive male rats after myocardial infarction","volume":"11","author":"Sudo","year":"2017","journal-title":"Drug Des. Devel Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.lfs.2014.06.002","article-title":"N-acylhydrazone improves exercise intolerance in rats submitted to myocardial infarction by the recovery of calcium homeostasis in skeletal muscle","volume":"94","author":"Pereira","year":"2014","journal-title":"Life Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"C1178","DOI":"10.1152\/ajpcell.00291.2008","article-title":"Regulation of cardiac fibroblast collagen synthesis by adenosine: Roles for Epac and PI3K","volume":"296","author":"Villarreal","year":"2009","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"096032712210776","DOI":"10.1177\/09603271221077684","article-title":"Shenfu Administration Improves Cardiac Fibrosis in Rats with Myocardial Ischemia-Reperfusion Through Adenosine A2a Receptor Activation","volume":"41","author":"Guo","year":"2022","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/nrd3431","article-title":"Novel therapeutic targets for the treatment of heart failure","volume":"10","author":"Tamargo","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1146\/annurev-immunol-020711-074942","article-title":"Neutrophil Function: From Mechanisms to Disease","volume":"30","author":"Amulic","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/CIRCRESAHA.116.303577","article-title":"The Biological Basis for Cardiac Repair After Myocardial Infarction","volume":"119","author":"Prabhu","year":"2016","journal-title":"Circ. Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Scalise, R.F.M., De Sarro, R., Caracciolo, A., Lauro, R., Squadrito, F., Carerj, S., Bitto, A., Micari, A., Di Bella, G., and Costa, F. (2021). Fibrosis after Myocardial Infarction: An Overview on Cellular Processes, Molecular Pathways, Clinical Evaluation and Prognostic Value. Med. Sci., 9.","DOI":"10.3390\/medsci9010016"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.yjmcc.2015.12.024","article-title":"The crossroads of inflammation, fibrosis, and arrhythmia following myocardial infarction","volume":"91","author":"Stuart","year":"2016","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_54","first-page":"724080","article-title":"Roles of TGF- \u03b2 Signals in Endothelial-Mesenchymal Transition during Cardiac Fibrosis","volume":"2011","author":"Yoshimatsu","year":"2011","journal-title":"Int. J. Inflam."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1042\/CS20171256","article-title":"Therapeutic effect of a novel Wnt pathway inhibitor on cardiac regeneration after myocardial infarction","volume":"131","author":"Yang","year":"2017","journal-title":"Clin. Sci. (Lon.)"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"22771","DOI":"10.1074\/jbc.272.36.22771","article-title":"Activation of the Hematopoietic Progenitor Kinase-1 (HPK1)-dependent, Stress-activated c-Jun N-terminal Kinase (JNK) Pathway by Transforming Growth Factor \u03b2 (TGF-\u03b2)-activated Kinase (TAK1), a Kinase Mediator of TGF \u03b2 Signal Transduction","volume":"272","author":"Wang","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41392-021-00762-6","article-title":"Wnt\/\u03b2-catenin signalling: Function, biological mechanisms, and therapeutic opportunities","volume":"7","author":"Liu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41401-018-0060-4","article-title":"Wnt signaling pathways in myocardial infarction and the therapeutic effects of Wnt pathway inhibitors","volume":"40","author":"Fu","year":"2019","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1091\/mbc.E19-03-0136","article-title":"Adenosine interaction with adenosine receptor A2a promotes gastric cancer metastasis by enhancing PI3K\u2013AKT\u2013mTOR signaling","volume":"30","author":"Shi","year":"2019","journal-title":"Mol. Biol. Cell"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Hemmings, B.A., and Restuccia, D.F. (2012). PI3K-PKB\/Akt Pathway. Cold Spring Harb. Perspect. Biol., 4.","DOI":"10.1101\/cshperspect.a011189"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.yjmcc.2017.07.011","article-title":"Entanglement of GSK-3\u03b2, \u03b2-catenin and TGF-\u03b21 signaling network to regulate myocardial fibrosis","volume":"110","author":"Guo","year":"2017","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1101\/gad.1590908","article-title":"Axin and GSK3-\u03b2 control Smad3 protein stability and modulate TGF-\u03b2 signaling","volume":"22","author":"Guo","year":"2008","journal-title":"Genes Dev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1161\/CIRCULATIONAHA.113.008364","article-title":"Cardiac Fibroblast Glycogen Synthase Kinase-3\u03b2 Regulates Ventricular Remodeling and Dysfunction in Ischemic Heart","volume":"130","author":"Lal","year":"2014","journal-title":"Circulation"},{"key":"ref_64","first-page":"1413","article-title":"Transforming growth factor-\u03b2-dependent Wnt secretion controls myofibroblast formation and myocardial fibrosis progression in experimental autoimmune myocarditis","volume":"38","author":"Blyszczuk","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"21110","DOI":"10.1073\/pnas.1004708107","article-title":"Exogenously administered secreted frizzled related protein 2 (Sfrp2) reduces fibrosis and improves cardiac function in a rat model of myocardial infarction","volume":"107","author":"He","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.yjmcc.2008.11.016","article-title":"Secreted frizzled related protein 2 protects cells from apoptosis by blocking the effect of canonical Wnt3a","volume":"46","author":"Zhang","year":"2009","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1242\/dmm.006510","article-title":"Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition","volume":"4","author":"Aisagbonhi","year":"2011","journal-title":"Dis. Model. Mech."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/emboj.2011.418","article-title":"Wnt1\/\u03b2catenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repair","volume":"31","author":"Duan","year":"2012","journal-title":"EMBO J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1016\/j.jcin.2020.08.007","article-title":"Effect of Ticagrelor on Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction (HEALING-AMI)","volume":"13","author":"Park","year":"2020","journal-title":"JACC Cardiovasc. Interv."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/24\/17546\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:40:02Z","timestamp":1760132402000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/24\/17546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,16]]},"references-count":69,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["ijms242417546"],"URL":"https:\/\/doi.org\/10.3390\/ijms242417546","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,16]]}}}