Redox environment metabolomic evaluation (REME) of the heart after myocardial ischemia/reperfusion injury

Wen-Bin Cai; Yin-Jiao Zhao; Le Liu; Qian Cheng; Jin Wang; Xue-Lian Shi; Liu Yao; Xin-Hua Qiao; Yi Zhu; Chang Chen; Xu Zhang

doi:10.1016/j.freeradbiomed.2021.06.033

Redox environment metabolomic evaluation (REME) of the heart after myocardial ischemia/reperfusion injury

Free Radic Biol Med. 2021 Sep:173:7-18. doi: 10.1016/j.freeradbiomed.2021.06.033. Epub 2021 Jul 9.

Authors

Wen-Bin Cai¹, Yin-Jiao Zhao¹, Le Liu¹, Qian Cheng¹, Jin Wang¹, Xue-Lian Shi¹, Liu Yao¹, Xin-Hua Qiao², Yi Zhu¹, Chang Chen³, Xu Zhang⁴

Affiliations

¹ Tianjin Key Laboratory of Metabolic Diseases, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Center for Cardiovascular Diseases, Research Center of Basic Medical Sciences, Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China.
² National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
³ National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. Electronic address: changchen@moon.ibp.ac.cn.
⁴ Tianjin Key Laboratory of Metabolic Diseases, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Center for Cardiovascular Diseases, Research Center of Basic Medical Sciences, Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China. Electronic address: xuzhang@tmu.edu.cn.

PMID: 34252540
DOI: 10.1016/j.freeradbiomed.2021.06.033

Abstract

Myocardial ischemia/reperfusion injury (MIRI) is closely related to oxidative stress. However, the redox environment of the heart has not been evaluated thoroughly after MIRI, which limits precise redox intervention. In this study, we developed the redox environment metabolomic evaluation (REME) method to analyze the redox metabolites of the heart after MIRI. Based on the targeted metabolomics strategy, we established a detection panel for 22 redox-related molecules, including the major redox couples nicotinamide adenine dinucleotide (NADH/NAD+), nicotinamide adenine dinucleotide phosphate (NADPH/NADP+), and glutathione/glutathione disulfide (GSH/GSSG), reactive oxygen and nitrogen species-related molecules, and some lipid peroxidation products. The high sensitivity and specificity of the method make it suitable for evaluating the endogenous redox environment. The REME method showed that the heart tissue in a MIRI mouse model had a different redox profile from that in the control group. Different redox species changed in different ways. The ratios of GSSG/GSH and NADP+/NADPH increased, but the levels of both NAD+ and NADH decreased in the risk area of the infarcted heart after reperfusion. In addition, some reactive nitrogen species-related metabolites (tetrahydrobiopterin, arginine, and S-nitrosoglutathione) decreased and some lipid peroxides (4-hydroxy-2-nonenal, 4-hydroxy-2-hexenal, and benzaldehyde) increased. The redox metabolites GSH, GSSG, NADPH, NAD+, S-nitrosoglutathione, arginine, and tetrahydrobiopterin had a positive correlation with the ejection fraction and a negative correlation with the level of lactate dehydrogenase in plasma. In summary, we achieved a comprehensive, systemic understanding of the changes in the redox environment after MIRI. Our REME method could be used to evaluate the redox environment in other processes.

Keywords: Lipid peroxidation products; Myocardial ischemia/reperfusion injury; Redox environment metabolic evaluation; Redox-related molecules.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Glutathione Disulfide / metabolism
Metabolomics
Mice
Myocardial Reperfusion Injury*
NADP / metabolism
Oxidation-Reduction

Substances

NADP
Glutathione Disulfide