{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:17:13Z","timestamp":1783487833380,"version":"3.55.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Myocardial fibrosis following myocardial infarction (MI) is a critical determinant of long-term clinical outcomes in heart disease. However, this central pathological process in the progression from MI to heart failure is not fully understood, posing challenges for targeted therapeutic options.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aimed to identify new targets critical to myocardial fibrosis after MI and to evaluate the potential of Guanxinning injection (GXNI, a combination of Danshen and Chuanxiong) to suppress post-MI myocardial fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A MI mouse model was established by permanent ligation of the left anterior descending artery. Therapeutic effects were assessed by echocardiography and histopathology. HPLC chromatography, Network pharmacology, molecular docking, two-dimensional primary cell cultures, and iPS-induced cardiac organoid models were employed to identify active components and investigate underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      GXNI reduced myocardial fibrosis and injury, improving cardiac function. Network pharmacology and molecular docking identified Senkyunolide I (SENI) and Danshensu (DSS) as the key active components acting via the TGF-\u03b21\/PAI-1 pathway. Thermal shift assay demonstrated direct binding of SENI and DSS to PAI-1.\n                      <jats:italic>In vitro<\/jats:italic>\n                      and cryoinjury cardiac organoid models confirmed that GXNI and the SENI-DSS combination inhibited fibroblast activation and TGF-\u03b21\/PAI-1 expression, reducing fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We demonstrate for the first time that the TGF-\u03b21\/PAI-1 signaling pathway plays a critical role in post-MI myocardial fibrosis, and GXNI attenuates MI via this pathway. Secondly, the active components of GXNI, SENI and DSS, act combinatorially to enhance the anti-fibrotic therapeutic efficacy. Furthermore, cryoinjury cardiac organoids serve as a powerful platform for investigating the mechanisms underlying myocardial infarction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1862471","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:40:51Z","timestamp":1783485651000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Senkyunolide I and Danshensu in combination ameliorate post-MI myocardial fibrosis by regulating TGF-\u03b21\/PAI-1 in mice and heart organoids"],"prefix":"10.3389","volume":"17","author":[{"given":"Siwen","family":"Fan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"Haihe Laboratory of Modern Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxu","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"Haihe Laboratory of Modern Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"Department of Pharmacy, China Academy of Chinese Medical Sciences, Guang\u2019anmen Hospital Jinan Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenan","family":"Nie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"Haihe Laboratory of Modern Chinese Medicine","place":["Tianjin, China"]},{"name":"College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"Haihe Laboratory of Modern Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linhong","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"Haihe Laboratory of Modern Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"Haihe Laboratory of Modern Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxu","family":"Xiao","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"National Clinical Research Center for Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"Haihe Laboratory of Modern Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s12013-014-0188-x","article-title":"Relation of PAI-1 and TPA genes polymorphisms to acute myocardial infarction and its outcomes in Egyptian patients","volume":"71","author":"Abd El-Aziz","year":"2015","journal-title":"Cell. Biochem. Biophys."},{"key":"B2","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1161\/circresaha.116.309202","article-title":"A simplified, langendorff-free method for concomitant isolation of viable cardiac myocytes and nonmyocytes from the adult mouse heart","volume":"119","author":"Ackers-Johnson","year":"2016","journal-title":"Circ. Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1165\/rcmb.2019-0341ED","article-title":"PAI-1: a new target for controlling lung-cell senescence and fibrosis?","volume":"62","author":"Adnot","year":"2020","journal-title":"Am. Journal Respiratory Cell Molecular Biology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41586-019-1546-z","article-title":"Targeting cardiac fibrosis with engineered T cells","volume":"573","author":"Aghajanian","year":"2019","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e596","DOI":"10.1161\/CIR.0000000000000678","article-title":"2019 ACC\/AHA guideline on the primary prevention of cardiovascular disease: a report of the American college of cardiology\/american heart association task force on clinical practice guidelines","volume":"140","author":"Arnett","year":"2019","journal-title":"Circulation"},{"key":"B6","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s00395-019-0722-5","article-title":"Inflammation and fibrosis in murine models of heart failure","volume":"114","author":"Bacmeister","year":"2019","journal-title":"Basic Research Cardiology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00395-020-00840-w","article-title":"Plasminogen activator inhibitor-1 reduces cardiac fibrosis and promotes M2 macrophage polarization in inflammatory cardiomyopathy","volume":"116","author":"Baumeier","year":"2021","journal-title":"Basic Research Cardiology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1161\/CIRCULATIONAHA.119.042960","article-title":"High-sensitivity cardiac troponin and the universal definition of myocardial infarction","volume":"141","author":"Chapman","year":"2020","journal-title":"Circulation"},{"key":"B9","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1161\/01.Cir.0000083471.33820.3c","article-title":"Acute release of plasminogen activator inhibitor-1 in ST-segment elevation myocardial infarction predicts mortality","volume":"108","author":"Collet","year":"2003","journal-title":"Circulation"},{"key":"B10","doi-asserted-by":"publisher","first-page":"3823","DOI":"10.1038\/s41467-025-59169-4","article-title":"Border-zone cardiomyocytes and macrophages regulate extracellular matrix remodeling to promote cardiomyocyte protrusion during cardiac regeneration","volume":"16","author":"Constanty","year":"2025","journal-title":"Nat. Commun."},{"key":"B11","doi-asserted-by":"publisher","first-page":"114642","DOI":"10.1016\/j.biopha.2023.114642","article-title":"Guanxinning injection ameliorates cardiac remodeling in HF mouse and 3D heart spheroid models via p38\/FOS\/MMP1-mediated inhibition of myocardial hypertrophy and fibrosis","volume":"162","author":"Fan","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1491582","DOI":"10.3389\/fphar.2025.1491582","article-title":"Qishen Yiqi alleviates periostin-mediated cardiac fibrosis and hypertrophy in Dahl hypertensive rat hearts and angiotensin II-induced cardiac organoids","volume":"16","author":"Fan","year":"","journal-title":"Front. Pharmacol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"157162","DOI":"10.1016\/j.phymed.2025.157162","article-title":"Protection against stroke-induced blood-brain barrier disruption by guanxinning injection and its active-component combination via TLR4\/NF-\u03baB\/MMP9-mediated neuroinflammation","volume":"147","author":"Fan","year":"","journal-title":"Phytomedicine"},{"key":"B14","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1055\/s-0036-1586228","article-title":"The role of plasminogen activator inhibitor Type-1 in fibrosis","volume":"43","author":"Flevaris","year":"2017","journal-title":"Semin. Thromb. Hemost."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1002\/cphy.c150006","article-title":"Pathophysiology of myocardial infarction","volume":"5","author":"Frangogiannis","year":"2015","journal-title":"Compr. Physiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1002\/jcp.22783","article-title":"PAI-1 in tissue fibrosis","volume":"227","author":"Ghosh","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"110555","DOI":"10.1016\/j.cellsig.2022.110555","article-title":"Cardiomyocyte PAI-1 influences the cardiac transcriptome and limits the extent of cardiac fibrosis in response to left ventricular pressure overload","volume":"104","author":"Ghosh","year":"2023","journal-title":"Cell. Signal"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1016\/j.jcmg.2024.03.012","article-title":"Cardiac magnetic resonance evaluation of LV remodeling post-myocardial infarction: prognosis, monitoring and trial endpoints","volume":"17","author":"Gissler","year":"2024","journal-title":"JACC Cardiovasc Imaging"},{"key":"B19","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1002\/ejhf.696","article-title":"Myocardial fibrosis: biomedical research from bench to bedside","volume":"19","author":"Gyongyosi","year":"2017","journal-title":"Eur. Journal Heart Failure"},{"key":"B20","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1136\/bjsports-2021-104876","article-title":"Cardiorespiratory fitness and mortality from all causes, cardiovascular disease and cancer: dose-response meta-analysis of cohort studies","volume":"56","author":"Han","year":"2022","journal-title":"Br. Journal Sports Medicine"},{"key":"B21","doi-asserted-by":"publisher","first-page":"3299","DOI":"10.1016\/j.cell.2021.04.034","article-title":"Cardioids reveal self-organizing principles of human cardiogenesis","volume":"184","author":"Hofbauer","year":"2021","journal-title":"Cell."},{"key":"B22","doi-asserted-by":"publisher","first-page":"5067","DOI":"10.3390\/ijms20205076","article-title":"Thrombin upregulates PAI-1 and mesothelial-mesenchymal transition through PAR-1 and contributes to tuberculous pleural fibrosis","volume":"20","author":"Hsieh","year":"2019","journal-title":"Int. Journal Molecular Sciences"},{"key":"B23","doi-asserted-by":"publisher","first-page":"53","DOI":"10.15887\/j.cnki.13-1389\/r.2025.18.013","article-title":"Clinical effect of Guanxin Ning injection combined with sacubitril valsartan sodium tablets in treating patients with coronary heart disease complicated with chronic heart failure and blood stasis obstruction syndrome","volume":"18","author":"Hu","year":"2025","journal-title":"Chin J Clin. Ration. Drug Use"},{"key":"B24","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1165\/rcmb.2011-0139OC","article-title":"Therapeutic value of small molecule inhibitor to plasminogen activator inhibitor-1 for lung fibrosis","volume":"46","author":"Huang","year":"2012","journal-title":"Am. Journal Respiratory Cell Molecular Biology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3636","DOI":"10.3390\/molecules28083636","article-title":"Senkyunolide I: a review of its phytochemistry, pharmacology, pharmacokinetics, and drug-likeness","volume":"28","author":"Huang","year":"2023","journal-title":"Molecules"},{"key":"B26","doi-asserted-by":"publisher","first-page":"114950","DOI":"10.1016\/j.bcp.2022.114950","article-title":"2,5-Dimethylcelecoxib attenuates cardiac fibrosis caused by cryoinjury-induced myocardial infarction by suppressing the fibroblast-to-myofibroblast transformation via inhibition of the TGF-\u03b2 signaling pathway","volume":"197","author":"Ikushima","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"282707","DOI":"10.1155\/2013\/282707","article-title":"The efficacy of guanxinning injection in treating angina pectoris: systematic review and meta-analysis of randomized controlled trials","volume":"2013","author":"Jia","year":"2013","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1001\/jamacardio.2020.6909","article-title":"Identification of cardiac fibrosis in young adults with a homozygous frameshift variant in SERPINE1","volume":"6","author":"Khan","year":"2021","journal-title":"JAMA Cardiology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"9128210","DOI":"10.1155\/2022\/9128210","article-title":"Loureirin B alleviates myocardial ischemia\/reperfusion injury via inhibiting PAI-1\/TGF-beta1\/Smad signaling pathway","volume":"2022","author":"Kong","year":"2022","journal-title":"Evidence-based Complementary Alternative Medicine eCAM."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.7150\/ijbs.7.1056","article-title":"Diverse roles of TGF-beta\/Smads in renal fibrosis and inflammation","volume":"7","author":"Lan","year":"2011","journal-title":"Int. Journal Biological Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"5142","DOI":"10.1038\/s41467-021-25329-5","article-title":"Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease","volume":"12","author":"Lewis-Israeli","year":"2021","journal-title":"Nat. Commun."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1159\/000447855","article-title":"Activation of cannabinoid receptor type II by AM1241 ameliorates myocardial fibrosis via Nrf2-Mediated inhibition of TGF-beta1\/Smad3 pathway in myocardial infarction mice","volume":"39","author":"Li","year":"2016","journal-title":"Cell. Physiology Biochem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.addr.2021.03.021","article-title":"Cardiac fibrosis: myofibroblast-mediated pathological regulation and drug delivery strategies","volume":"173","author":"Liu","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"157662","DOI":"10.1016\/j.phymed.2025.157662","article-title":"Tetramethylpyrazine alleviates ventricular remodeling after myocardial infarction by regulating Sirt1\/p300\/Yy1\/sST2 signaling axis","volume":"150","author":"Liu","year":"2026","journal-title":"Phytomedicine"},{"key":"B35","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1248\/bpb.b13-00921","article-title":"Danshensu inhibits \u03b2-adrenergic receptors-mediated cardiac fibrosis by ROS\/p38 MAPK axis","volume":"37","author":"Lu","year":"2014","journal-title":"Biol. Pharm. Bull."},{"key":"B36","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.yjmcc.2020.12.001","article-title":"Gut microbiome - a potential mediator of pathogenesis in heart failure and its comorbidities: state-of-the-art review","volume":"152","author":"Mamic","year":"2021","journal-title":"J. Mol. Cell. Cardiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"113587","DOI":"10.1016\/j.intimp.2024.113587","article-title":"PAI-1 influences and curcumin destabilizes MMP-2, MMP-9 and basement membrane proteins during lung injury and fibrosis","volume":"143","author":"Moideen","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1161\/circresaha.124.325488","article-title":"Renal-cardiac crosstalk in the pathogenesis and progression of heart failure","volume":"136","author":"Noels","year":"2025","journal-title":"Circ. Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s12943-022-01569-x","article-title":"Targeting TGF-beta signal transduction for fibrosis and cancer therapy","volume":"21","author":"Peng","year":"2022","journal-title":"Mol. Cancer"},{"key":"B40","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1161\/circresaha.116.303577","article-title":"The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis","volume":"119","author":"Prabhu","year":"2016","journal-title":"Circ. Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1002\/jcb.26146","article-title":"Plasminogen activator inhibitor Type-1 as a regulator of fibrosis","volume":"119","author":"Rabieian","year":"2018","journal-title":"J. Cellular Biochemistry"},{"key":"B42","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1165\/rcmb.2019-0071OC","article-title":"PAI-1 regulation of TGF-beta1-induced alveolar type II cell senescence, SASP secretion, and SASP-mediated activation of alveolar macrophages","volume":"62","author":"Rana","year":"2020","journal-title":"Am. Journal Respiratory Cell Molecular Biology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.jaci.2016.02.028","article-title":"TGF-beta1-induced PAI-1 contributes to a profibrotic network in patients with eosinophilic esophagitis","volume":"138","author":"Rawson","year":"2016","journal-title":"J. Allergy Clinical Immunology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1093\/cvr\/cvz300","article-title":"In peripartum cardiomyopathy plasminogen activator inhibitor-1 is a potential new biomarker with controversial roles","volume":"116","author":"Ricke-Hoch","year":"2020","journal-title":"Cardiovasc. Research"},{"key":"B45","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.jpba.2011.10.007","article-title":"Qualitative and quantitative analysis of the major constituents in Chinese medicinal preparation Guan-Xin-Ning injection by HPLC-DAD-ESI-MS(n)","volume":"59","author":"Ruan","year":"2012","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B46","doi-asserted-by":"publisher","first-page":"557","DOI":"10.5551\/jat.32300","article-title":"Myocardial production of plasminogen activator Inhibitor-1 is associated with coronary endothelial and ventricular dysfunction after acute myocardial infarction","volume":"23","author":"Shimizu","year":"2016","journal-title":"J. Atheroscler. Thromb."},{"key":"B47","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.yjmcc.2013.11.015","article-title":"Fibroblasts in myocardial infarction: a role in inflammation and repair","volume":"70","author":"Shinde","year":"2014","journal-title":"J. Molecular Cellular Cardiology"},{"key":"B48","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1253\/jcj.64.547","article-title":"Plasma and platelet plasminogen activator inhibitor-1 in patients with acute myocardial infarction","volume":"64","author":"Soeki","year":"2000","journal-title":"Jpn. Circ. J."},{"key":"B49","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/S0002-9440(10)63135-5","article-title":"Increased expression of plasminogen activator inhibitor-1 in cardiomyocytes contributes to cardiac fibrosis after myocardial infarction","volume":"164","author":"Takeshita","year":"2004","journal-title":"Am. J. Pathology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1832","DOI":"10.1161\/circulationaha.116.024145","article-title":"Defined engineered human myocardium with advanced maturation for applications in heart failure modeling and repair","volume":"135","author":"Tiburcy","year":"2017","journal-title":"Circulation"},{"key":"B51","doi-asserted-by":"publisher","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 Journal"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1161\/circresaha.115.306565","article-title":"Cardiac fibrosis: the fibroblast awakens","volume":"118","author":"Travers","year":"2016","journal-title":"Circ. Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.thromres.2012.06.023","article-title":"The biochemistry, physiology and pathological roles of PAI-1 and the requirements for PAI-1 inhibition in vivo","volume":"130","author":"Van De Craen","year":"2012","journal-title":"Thrombosis Research"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1111\/j.1538-7836.2005.01420.x","article-title":"PAI-1 and atherothrombosis","volume":"3","author":"Vaughan","year":"2005","journal-title":"J. Thrombosis Haemostasis"},{"key":"B55","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1161\/01.ATV.0000209949.86606.c2","article-title":"PAI-1 and TGF-beta: unmasking the real driver of TGF-beta-induced vascular pathology","volume":"26","author":"Vaughan","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.3390\/cells11091386","article-title":"Properties and functions of fibroblasts and myofibroblasts in myocardial infarction","volume":"11","author":"Venugopal","year":"2022","journal-title":"Cells"},{"key":"B57","doi-asserted-by":"publisher","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart disease and stroke Statistics-2021 update: a report from the American heart association","volume":"143","author":"Virani","year":"2021","journal-title":"Circulation"},{"key":"B58","doi-asserted-by":"publisher","first-page":"C1260","DOI":"10.1152\/ajpcell.00345.2021","article-title":"In vitro cell cultures of Brunner's glands from male mouse to study GLP-1 receptor function","volume":"322","author":"Voetmann","year":"2022","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"402","DOI":"10.27023\/j.cnki.1001-5183.2026.03.016","article-title":"Efficacy of guanxinning injection for coronary heart disease with congestive heart Fa","volume":"56","author":"Wang","year":"2026","journal-title":"Xinjiang Medical Journal."},{"key":"B60","doi-asserted-by":"publisher","first-page":"905254","DOI":"10.3389\/fcvm.2022.905254","article-title":"Guanxinning injection combined with ischemic postconditioning attenuate myocardial ischemic reperfusion injury in chronic renal failure rats by modulating mitochondrial dynamics","volume":"9","author":"Wang","year":"2022","journal-title":"Front. Cardiovasc Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"114516","DOI":"10.1016\/j.jpba.2021.114516","article-title":"Urinary metabolomics analysis to reveal metabolic mechanism of guanxinning injection on heart failure with renal dysfunction","volume":"209","author":"Wang","year":"2022","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B62","doi-asserted-by":"publisher","first-page":"116367","DOI":"10.1016\/j.jep.2023.116367","article-title":"Guanxining injection alleviates fibrosis in heart failure mice and regulates SLC7A11\/GPX4 axis","volume":"310","author":"Wang","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"735","DOI":"10.3389\/fphar.2019.00735","article-title":"Ginkgo flavonol glycosides or ginkgolides tend to differentially protect myocardial or cerebral ischemia-reperfusion injury via regulation of TWEAK-Fn14 signaling in heart and brain","volume":"10","author":"Xiao","year":"2019","journal-title":"Front. Pharmacol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1007341","DOI":"10.3389\/fimmu.2022.1007341","article-title":"CXCR1 and its downstream NF-kappaB inflammation signaling pathway as a key target of Guanxinning injection for myocardial ischemia\/reperfusion injury","volume":"13","author":"Xiao","year":"2022","journal-title":"Front. Immunology"},{"key":"B64","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1182\/blood-2009-09-244962","article-title":"Plasminogen activator inhibitor-1 (PAI-1) is cardioprotective in mice by maintaining microvascular integrity and cardiac architecture","volume":"115","author":"Xu","year":"2010","journal-title":"Blood"},{"key":"B65","doi-asserted-by":"publisher","first-page":"e00299","DOI":"10.1002\/advs.202500299","article-title":"Injectable BMSC-based extracellular matrix-mimicking microtissue for myocardial infarction repair","volume":"13","author":"Yao","year":"2026","journal-title":"Adv. Sci. (Weinh)"},{"key":"B66","doi-asserted-by":"publisher","first-page":"246","DOI":"10.3181\/0811-RM-321","article-title":"A profibrotic effect of plasminogen activator inhibitor type-1 (PAI-1) in the heart","volume":"234","author":"Zaman","year":"2009","journal-title":"Exp. Biology Medicine"},{"key":"B67","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1186\/s12967-024-05624-7","article-title":"Identification of macrophage driver genes in fibrosis caused by different heart diseases based on omics integration","volume":"22","author":"Zhang","year":"2024","journal-title":"J. Transl. Med."},{"key":"B68","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1038\/labinvest.2014.51","article-title":"Vitronectin-binding PAI-1 protects against the development of cardiac fibrosis through interaction with fibroblasts","volume":"94","author":"Zhong","year":"2014","journal-title":"Laboratory Invest. J. Techn. Methods Path."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1862471\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:41:00Z","timestamp":1783485660000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1862471\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":69,"alternative-id":["10.3389\/fphar.2026.1862471"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1862471","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]},"article-number":"1862471"}}