{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T12:56:38Z","timestamp":1780664198103,"version":"3.54.1"},"reference-count":32,"publisher":"IMR Press","issue":"1","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Myocardial ischemia-reperfusion (I\/R) injury and coronary microcirculation dysfunction (CMD) are observed in patients with myocardial infarction after vascular recanalization. The antianginal drug trimetazidine has been demonstrated to exert a protective effect in myocardial ischemia-reperfusion injury. Objectives: This study aimed to investigate the role of trimetazidine in endothelial cell dysfunction caused by myocardial I\/R injury and thus improve coronary microcirculation. Methods: The myocardial I\/R mouse model was established, and trimetazidine was administered for 7 days before myocardial I\/R model establishment. Echocardiography, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&amp;E) staining, and thioflavin S staining were applied to assess myocardial injury and microvascular function. Additionally, the oxygen-glucose deprivation\/reperfusion (OGD\/R) model was developed in endothelial cells to simulate myocardial I\/R injury in vitro. Griess reaction method, immunofluorescence, and western blotting (WB) were employed to detect the expressions of nitric oxide (NO), platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial (VE)-cadherin, zonula occludens protein 1 (ZO-1), occludin, vascular endothelial growth factor (VEGF) and adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling-related proteins in endothelial cells and mouse cardiomyocytes. AMPK pathway inhibitor compound C was used for further mechanism validation. Results: Our research demonstrated that trimetazidine can alleviate myocardial pathological injury and cardiac function injury during myocardial I\/R. Trimetazidine was observed to improve microvascular reflux phenomenon and microvascular function and barrier injury in myocardial I\/R and OGD\/R models. Additionally, the expressions of AMPK signal-related proteins were found to be inhibited in myocardial I\/R and OGD\/R models, which were then activated in mice administered trimetazidine. However, the effects of trimetazidine on endothelial cell function and barrier damage were attenuated after co-treatment with compound C and trimetazidine. Conclusion: Trimetazidine ameliorated myocardial I\/R-induced CMD by activating AMPK signaling.<\/jats:p>","DOI":"10.31083\/fbl25565","type":"journal-article","created":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T08:54:32Z","timestamp":1737795272000},"source":"Crossref","is-referenced-by-count":6,"title":["Trimetazidine: Activating AMPK Signal to Ameliorate Coronary Microcirculation Dysfunction after Myocardial Infarction"],"prefix":"10.31083","volume":"30","author":[{"given":"Xiaolong","family":"Qu","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, 401336 Chongqing, China"},{"name":"Department of Cardiovascular Medicine, Southwest Hospital, Army Medical University, 400038 Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Yang","sequence":"first","affiliation":[{"name":"Emergency Department, The Second Affiliated Hospital of Chongqing Medical University, 401336 Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jiao","sequence":"first","affiliation":[{"name":"Department of High Altitude Physiology and Pathology, College of High Altitude Military Medicine, Army Military Medical University, 400037 Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9769-435X","authenticated-orcid":true,"given":"Yuehui","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, 401336 Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Abdu FA, Mohammed AQ, Liu L, Xu Y, Che W. 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