PMID- 37525913
OWN - NLM
STAT- Publisher
LR  - 20230801
IS  - 2768-6698 (Electronic)
IS  - 2768-6698 (Linking)
VI  - 28
IP  - 7
DP  - 2023 Jul 19
TI  - A Metabolomics-Based Study on NMDAR-Mediated Mitochondrial Damage through Calcium 
      Overload and ROS Accumulation in Myocardial Infarction.
PG  - 140
LID - 10.31083/j.fbl2807140 [doi]
AB  - 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)-related 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-induced 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 < 0.05). Mitochondrial 
      damage-induced apoptosis was significantly inhibited by a selective NDMAR 
      antagonist (p < 0.05), while Bax expression was remarkably decreased and Bcl-2 
      expression was increased (p < 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 < 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.
CI  - (c) 2023 The Author(s). Published by IMR Press.
FAU - Wang, Yuanyuan
AU  - Wang Y
AD  - Department of Cardiovascular Surgery, West China Hospital, Sichuan University, 
      610007 Chengdu, Sichuan, China.
FAU - He, Li
AU  - He L
AD  - Department of Cardiovascular Surgery, West China Hospital, Sichuan University, 
      610007 Chengdu, Sichuan, China.
AD  - Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan 
      University, 610007 Chengdu, Sichuan, China.
FAU - Du, Dan
AU  - Du D
AD  - West China - Washington Mitochondria and Metabolism Center, West China Hospital, 
      Sichuan University, 610007 Chengdu, Sichuan, China.
FAU - Cheng, Zeyi
AU  - Cheng Z
AD  - Department of Cardiovascular Surgery, West China Hospital, Sichuan University, 
      610007 Chengdu, Sichuan, China.
FAU - Qin, Chaoyi
AU  - Qin C
AD  - Department of Cardiovascular Surgery, West China Hospital, Sichuan University, 
      610007 Chengdu, Sichuan, China.
AD  - Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan 
      University, 610007 Chengdu, Sichuan, China.
LA  - eng
GR  - 81900311/National Natural Science Foundation of China/
GR  - 2022YFS0364/Science and Technology Agency Foundation of Sichuan province/
PT  - Journal Article
PL  - Singapore
TA  - Front Biosci (Landmark Ed)
JT  - Frontiers in bioscience (Landmark edition)
JID - 101612996
SB  - IM
OTO - NOTNLM
OT  - NMDAR
OT  - calcium overload
OT  - metabolomics
OT  - mitochondrial damage
OT  - myocardial infarction
COIS- The authors declare no conflict of interest.
EDAT- 2023/08/01 06:45
MHDA- 2023/08/01 06:45
CRDT- 2023/08/01 03:52
PHST- 2022/12/12 00:00 [received]
PHST- 2023/03/16 00:00 [revised]
PHST- 2023/03/21 00:00 [accepted]
PHST- 2023/08/01 06:45 [medline]
PHST- 2023/08/01 06:45 [pubmed]
PHST- 2023/08/01 03:52 [entrez]
AID - S2768-6701(23)00843-2 [pii]
AID - 10.31083/j.fbl2807140 [doi]
PST - ppublish
SO  - Front Biosci (Landmark Ed). 2023 Jul 19;28(7):140. doi: 10.31083/j.fbl2807140.