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(Landmark Ed)"],"abstract":"<jats:p>Background: Coronary artery disease is a leading public health problem. However, the mechanisms underlying mitochondrial damage remain unclear. The present study verified and explored the novel mechanisms underlying ischemic injury based on a metabolomic analysis. Methods: Mouse models of acute myocardial infarction were established, and serum samples were collected for targeted liquid chromatography with tandem mass spectrometry analysis. Based on metabolomic analyses, the N-methyl-d-aspartic acid receptor (NMDAR)\u2013related calcium transporting signaling pathway was selected. Primary cardiomyocyte cultures were used, and N-methyl-d-aspartic acid (NMDA) was used as an agonist to confirm the role of NMDAR in ischemic injury. In addition, Bax, Bcl-2, mitochondrial calcium, potential, and mitochondrial reactive oxygen species accumulation were used to explore the role of NMDAR in mitochondrial damage\u2013induced apoptosis. Results: Glutamate-related metabolism was significantly altered following in acute myocardial infarction. NMDA induces apoptosis under hypoxic conditions NMDAR was translocated to the mitochondrial-related membrane after activation, and its mitochondrial expression was significantly increased (p &lt; 0.05). Mitochondrial damage\u2013induced apoptosis was significantly inhibited by a selective NDMAR antagonist (p &lt; 0.05), while Bax expression was remarkably decreased and Bcl-2 expression was increased (p &lt; 0.05). To further explore the mechanism of NMDAR, mitochondrial calcium, membrane potential, and reactive oxygen species were detected. With NMDAR inhibition under hypoxic conditions, mitochondrial morphology and function were preserved (p &lt; 0.05). Conclusions: Our metabolomic study identified NMDAR as a promising target. In conclusion, our study provides solid data for further studies of the role of NMDAR in cardiovascular diseases and a promising target to interfere with apoptosis in acute myocardial infarction.<\/jats:p>","DOI":"10.31083\/j.fbl2807140","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T08:24:20Z","timestamp":1689927860000},"source":"Crossref","is-referenced-by-count":6,"title":["A Metabolomics-Based Study on NMDAR-Mediated Mitochondrial Damage through Calcium Overload and ROS Accumulation in Myocardial Infarction"],"prefix":"10.31083","volume":"28","author":[{"given":"Yuanyuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, West China Hospital, Sichuan University, 610007 Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"He","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, West China Hospital, Sichuan University, 610007 Chengdu, Sichuan, China"},{"name":"Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan University, 610007 Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Du","sequence":"first","affiliation":[{"name":"West China - Washington Mitochondria and Metabolism Center, West China Hospital, Sichuan University, 610007 Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyi","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, West China Hospital, Sichuan University, 610007 Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyi","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, West China Hospital, Sichuan University, 610007 Chengdu, Sichuan, China"},{"name":"Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan University, 610007 Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Liu YT, Zhou C, Jia HM, Chang X, Zou ZM. 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