RETRACTED ARTICLE: Protective role of arachidonic acid against diabetic myocardial ischemic injury: a translational study of pigs, rats, and humans
Abstract Aim Patients with diabetes mellitus have poor prognosis after myocardial ischemic injury. However, the mechanism is unclear and there are no related therapies. We aimed to identify regulators of diabetic myocardial ischemic injury. Methods and results Mass spectrometry-based, non-targeted m...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-024-02123-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849420474603274240 |
|---|---|
| author | Yunhui Lv Kai Li Shuo Wang Xiaokang Wang Guangxin Yue Yangyang Zhang Xin Lv Ping Zhao Shiping Wang Qi Zhang Qiuju Li Jinyan Zhu Jubo Li Peng Peng Yue Li Jiafei Luo Xue Zhang Jianzhong Yang Baojie Zhang Xuemin Wang Min Zhang Chen Shen Xin Wang Miao Wang Zhen Ye Yongchun Cui |
| author_facet | Yunhui Lv Kai Li Shuo Wang Xiaokang Wang Guangxin Yue Yangyang Zhang Xin Lv Ping Zhao Shiping Wang Qi Zhang Qiuju Li Jinyan Zhu Jubo Li Peng Peng Yue Li Jiafei Luo Xue Zhang Jianzhong Yang Baojie Zhang Xuemin Wang Min Zhang Chen Shen Xin Wang Miao Wang Zhen Ye Yongchun Cui |
| author_sort | Yunhui Lv |
| collection | DOAJ |
| description | Abstract Aim Patients with diabetes mellitus have poor prognosis after myocardial ischemic injury. However, the mechanism is unclear and there are no related therapies. We aimed to identify regulators of diabetic myocardial ischemic injury. Methods and results Mass spectrometry-based, non-targeted metabolomic approach was used to profile coronary sinus blood from diabetic and non-diabetic Bama-mini pigs at 0.5-h post coronary artery ligation. Six metabolites had a |log2 (Fold Change)|> 1.3. Among them, the most changed is arachidonic acid (AA), levels of which were 32 times lower in diabetic pigs than in non-diabetic pigs. The AA-derived products, PGI2 and 6-keto-PGF1α, were also significantly reduced. AA treatment of cultured cardiomyocytes protected against cell death by 30% at 48 h of high glucose and oxygen deprivation, which coincided with increased mitophagic activity (as indicated by increased LC3II/LC3I, decreased p62 and increased parkin & PINK1), improved mitochondrial renewal (upregulation of Drp1 and FIS1), reduced ROS generation and increased ATP production. These cardioprotective effects were abolished by PINK1(a crucial mitophagy protein) knockdown or the autophagy inhibitor 3-Methyladenine. The protective effect of AA was also inhibited by indomethacin and Cay10441, a prostacyclin receptor antagonist. Furthermore, diabetic Sprague Dawley rats were subjected to coronary ligation for 40 min and AA treatment (10 mg/day per animal gavaged) decreased myocardial infarct size, cell apoptosis index, inflammatory cytokines and improved heart function. Scanning electron microscopy showed more intact mitochondria in the border zone of infarcted myocardium in AA treated rats. Lastly, diabetic patients after myocardial infarction had lower plasma levels of AA and 6-keto-PGF1α and reduced cardiac ejection fraction, compared with non-diabetic patients after myocardial infarction. Plasma AA level was inversely correlated with fasting blood glucose. Conclusions AA protects against diabetic ischemic myocardial damage by promoting mitochondrial autophagy and renewal, which is related to AA derived PGI2 signaling. AA may represent a new strategy to treat diabetic myocardial ischemic injury. |
| format | Article |
| id | doaj-art-cc7c9d64c1874f3180bcdb9f4595ec68 |
| institution | Kabale University |
| issn | 1475-2840 |
| language | English |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj-art-cc7c9d64c1874f3180bcdb9f4595ec682025-08-20T03:31:45ZengBMCCardiovascular Diabetology1475-28402024-02-0123111710.1186/s12933-024-02123-3RETRACTED ARTICLE: Protective role of arachidonic acid against diabetic myocardial ischemic injury: a translational study of pigs, rats, and humansYunhui Lv0Kai Li1Shuo Wang2Xiaokang Wang3Guangxin Yue4Yangyang Zhang5Xin Lv6Ping Zhao7Shiping Wang8Qi Zhang9Qiuju Li10Jinyan Zhu11Jubo Li12Peng Peng13Yue Li14Jiafei Luo15Xue Zhang16Jianzhong Yang17Baojie Zhang18Xuemin Wang19Min Zhang20Chen Shen21Xin Wang22Miao Wang23Zhen Ye24Yongchun Cui25Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Pharmacy & Cardiology & Endocrinology & General Surgery, Suqian First HospitalDepartment of Pharmacy & Cardiology & Endocrinology & General Surgery, Suqian First HospitalDepartment of Pharmacy & Cardiology & Endocrinology & General Surgery, Suqian First HospitalDepartment of Pharmacy & Cardiology & Endocrinology & General Surgery, Suqian First HospitalFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeFuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Aim Patients with diabetes mellitus have poor prognosis after myocardial ischemic injury. However, the mechanism is unclear and there are no related therapies. We aimed to identify regulators of diabetic myocardial ischemic injury. Methods and results Mass spectrometry-based, non-targeted metabolomic approach was used to profile coronary sinus blood from diabetic and non-diabetic Bama-mini pigs at 0.5-h post coronary artery ligation. Six metabolites had a |log2 (Fold Change)|> 1.3. Among them, the most changed is arachidonic acid (AA), levels of which were 32 times lower in diabetic pigs than in non-diabetic pigs. The AA-derived products, PGI2 and 6-keto-PGF1α, were also significantly reduced. AA treatment of cultured cardiomyocytes protected against cell death by 30% at 48 h of high glucose and oxygen deprivation, which coincided with increased mitophagic activity (as indicated by increased LC3II/LC3I, decreased p62 and increased parkin & PINK1), improved mitochondrial renewal (upregulation of Drp1 and FIS1), reduced ROS generation and increased ATP production. These cardioprotective effects were abolished by PINK1(a crucial mitophagy protein) knockdown or the autophagy inhibitor 3-Methyladenine. The protective effect of AA was also inhibited by indomethacin and Cay10441, a prostacyclin receptor antagonist. Furthermore, diabetic Sprague Dawley rats were subjected to coronary ligation for 40 min and AA treatment (10 mg/day per animal gavaged) decreased myocardial infarct size, cell apoptosis index, inflammatory cytokines and improved heart function. Scanning electron microscopy showed more intact mitochondria in the border zone of infarcted myocardium in AA treated rats. Lastly, diabetic patients after myocardial infarction had lower plasma levels of AA and 6-keto-PGF1α and reduced cardiac ejection fraction, compared with non-diabetic patients after myocardial infarction. Plasma AA level was inversely correlated with fasting blood glucose. Conclusions AA protects against diabetic ischemic myocardial damage by promoting mitochondrial autophagy and renewal, which is related to AA derived PGI2 signaling. AA may represent a new strategy to treat diabetic myocardial ischemic injury.https://doi.org/10.1186/s12933-024-02123-3Arachidonic acidMyocardial ischemic injuryDiabetes mellitusProstaglandin |
| spellingShingle | Yunhui Lv Kai Li Shuo Wang Xiaokang Wang Guangxin Yue Yangyang Zhang Xin Lv Ping Zhao Shiping Wang Qi Zhang Qiuju Li Jinyan Zhu Jubo Li Peng Peng Yue Li Jiafei Luo Xue Zhang Jianzhong Yang Baojie Zhang Xuemin Wang Min Zhang Chen Shen Xin Wang Miao Wang Zhen Ye Yongchun Cui RETRACTED ARTICLE: Protective role of arachidonic acid against diabetic myocardial ischemic injury: a translational study of pigs, rats, and humans Cardiovascular Diabetology Arachidonic acid Myocardial ischemic injury Diabetes mellitus Prostaglandin |
| title | RETRACTED ARTICLE: Protective role of arachidonic acid against diabetic myocardial ischemic injury: a translational study of pigs, rats, and humans |
| title_full | RETRACTED ARTICLE: Protective role of arachidonic acid against diabetic myocardial ischemic injury: a translational study of pigs, rats, and humans |
| title_fullStr | RETRACTED ARTICLE: Protective role of arachidonic acid against diabetic myocardial ischemic injury: a translational study of pigs, rats, and humans |
| title_full_unstemmed | RETRACTED ARTICLE: Protective role of arachidonic acid against diabetic myocardial ischemic injury: a translational study of pigs, rats, and humans |
| title_short | RETRACTED ARTICLE: Protective role of arachidonic acid against diabetic myocardial ischemic injury: a translational study of pigs, rats, and humans |
| title_sort | retracted article protective role of arachidonic acid against diabetic myocardial ischemic injury a translational study of pigs rats and humans |
| topic | Arachidonic acid Myocardial ischemic injury Diabetes mellitus Prostaglandin |
| url | https://doi.org/10.1186/s12933-024-02123-3 |
| work_keys_str_mv | AT yunhuilv retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT kaili retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT shuowang retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT xiaokangwang retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT guangxinyue retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT yangyangzhang retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT xinlv retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT pingzhao retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT shipingwang retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT qizhang retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT qiujuli retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT jinyanzhu retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT juboli retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT pengpeng retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT yueli retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT jiafeiluo retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT xuezhang retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT jianzhongyang retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT baojiezhang retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT xueminwang retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT minzhang retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT chenshen retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT xinwang retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT miaowang retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT zhenye retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans AT yongchuncui retractedarticleprotectiveroleofarachidonicacidagainstdiabeticmyocardialischemicinjuryatranslationalstudyofpigsratsandhumans |