Frontiers in Pharmacology (Mar 2020)
Aldehyde Dehydrogenase 2 Protects Against Post-Cardiac Arrest Myocardial Dysfunction Through a Novel Mechanism of Suppressing Mitochondrial Reactive Oxygen Species Production
- Rui Zhang,
- Rui Zhang,
- Rui Zhang,
- Rui Zhang,
- Baoshan Liu,
- Baoshan Liu,
- Baoshan Liu,
- Baoshan Liu,
- Xinhui Fan,
- Xinhui Fan,
- Xinhui Fan,
- Xinhui Fan,
- Wenjun Wang,
- Wenjun Wang,
- Wenjun Wang,
- Wenjun Wang,
- Tonghui Xu,
- Tonghui Xu,
- Tonghui Xu,
- Tonghui Xu,
- Shujian Wei,
- Shujian Wei,
- Shujian Wei,
- Shujian Wei,
- Wen Zheng,
- Wen Zheng,
- Wen Zheng,
- Wen Zheng,
- Qiuhuan Yuan,
- Qiuhuan Yuan,
- Qiuhuan Yuan,
- Qiuhuan Yuan,
- Luyao Gao,
- Luyao Gao,
- Luyao Gao,
- Luyao Gao,
- Xinxin Yin,
- Xinxin Yin,
- Xinxin Yin,
- Xinxin Yin,
- Boyuan Zheng,
- Boyuan Zheng,
- Boyuan Zheng,
- Boyuan Zheng,
- Chuanxin Zhang,
- Chuanxin Zhang,
- Chuanxin Zhang,
- Chuanxin Zhang,
- Shuai Zhang,
- Shuai Zhang,
- Shuai Zhang,
- Shuai Zhang,
- Kehui Yang,
- Kehui Yang,
- Kehui Yang,
- Kehui Yang,
- Mengyang Xue,
- Mengyang Xue,
- Mengyang Xue,
- Mengyang Xue,
- Shuo Wang,
- Shuo Wang,
- Shuo Wang,
- Shuo Wang,
- Feng Xu,
- Feng Xu,
- Feng Xu,
- Feng Xu,
- Jiali Wang,
- Jiali Wang,
- Jiali Wang,
- Jiali Wang,
- Yihai Cao,
- Yuguo Chen,
- Yuguo Chen,
- Yuguo Chen,
- Yuguo Chen
Affiliations
- Rui Zhang
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Rui Zhang
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Rui Zhang
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Rui Zhang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Baoshan Liu
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Baoshan Liu
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Baoshan Liu
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Baoshan Liu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Xinhui Fan
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Xinhui Fan
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Xinhui Fan
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Xinhui Fan
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Wenjun Wang
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Wenjun Wang
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Wenjun Wang
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Wenjun Wang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Tonghui Xu
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Tonghui Xu
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Tonghui Xu
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Tonghui Xu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Shujian Wei
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Shujian Wei
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Shujian Wei
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Shujian Wei
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Wen Zheng
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Wen Zheng
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Wen Zheng
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Wen Zheng
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Qiuhuan Yuan
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Qiuhuan Yuan
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Qiuhuan Yuan
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Qiuhuan Yuan
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Luyao Gao
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Luyao Gao
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Luyao Gao
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Luyao Gao
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Xinxin Yin
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Xinxin Yin
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Xinxin Yin
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Xinxin Yin
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Boyuan Zheng
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Boyuan Zheng
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Boyuan Zheng
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Boyuan Zheng
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Chuanxin Zhang
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Chuanxin Zhang
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Chuanxin Zhang
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Chuanxin Zhang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Shuai Zhang
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Shuai Zhang
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Shuai Zhang
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Shuai Zhang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Kehui Yang
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Kehui Yang
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Kehui Yang
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Kehui Yang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Mengyang Xue
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Mengyang Xue
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Mengyang Xue
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Mengyang Xue
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Shuo Wang
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Shuo Wang
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Shuo Wang
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Shuo Wang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Feng Xu
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Feng Xu
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Feng Xu
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Feng Xu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Jiali Wang
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Jiali Wang
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Jiali Wang
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Jiali Wang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- Yihai Cao
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden
- Yuguo Chen
- Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China
- Yuguo Chen
- Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China
- Yuguo Chen
- Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China
- Yuguo Chen
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China
- DOI
- https://doi.org/10.3389/fphar.2020.00373
- Journal volume & issue
-
Vol. 11
Abstract
Post-cardiac arrest myocardial dysfunction significantly contributes to early mortality after the return of spontaneous circulation. However, no effective therapy is available now. Aldehyde dehydrogenase 2 (ALDH2) enzyme has been shown to protect the heart from aldehyde toxicity such as 4-hydroxy-2-nonenal (4-HNE) and oxidative stress. In this study, we evaluated the effect of enhanced activity or expression of ALDH2 on post-cardiac arrest myocardial dysfunction and survival in a rat cardiac arrest model. Furthermore, we elucidated the underlying mechanisms with a focus on mitochondrial reactive oxygen species (ROS) production in a cell hypoxia/reoxygenation model. A total of 126 rats were used for the ALDH2 activation or cardiac overexpression of ALDH2 studies. Randomization was done 10 min before the respective agonist injection or in vivo gene delivery. We showed that enhanced activity or expression of ALDH2 significantly improved contractile function of the left ventricle and survival rate in rats subjected to cardiac arrest-cardiopulmonary resuscitation procedure. Moreover, ALDH2 prevented cardiac arrest-induced cardiomyocyte death from apoptosis and mitochondrial damage. Mechanistically, 4-HNE, a representative substrate of ALDH2, was dominantly increased in the hypoxia/reoxygenation-exposed cardiomyocytes. Direct addition of 4-HNE led to significantly augmented succinate accumulation and mitochondrial ROS production. Through metabolizing 4-HNE, ALDH2 significantly inhibited mitochondrial ROS production. Our findings provide compelling evidence of the cardioprotective effects of ALDH2 and therapeutic targeting this enzyme would provide an important approach for treating post-cardiac arrest myocardial dysfunction.
Keywords
- aldehyde dehydrogenase 2
- cardiopulmonary resuscitation
- post-cardiac arrest myocardial dysfunction
- cardiomyocyte death
- mitochondrial reactive oxygen species
