期刊
REDOX BIOLOGY
卷 26, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.redox.2019.101292
关键词
Oxidative stress; Tocopherol; ROS-Sensitive nanoprobe; Myocardial infarction; Ischemia/reperfusion injury
资金
- Deutsche Forschungsgemeinschaft (DFG) [Wa 3836/1-1]
- Australian Research Training Program Scholarship
- National Heart Foundation of Australia Future Leader Fellowship
- National Health and Medical Research council (NHMRC) of Australia [GNT1079492, GNT1163507]
- Victorian Government's Operational Infrastructure Support Program
- Forschungskreis der Ernahrungsindustrie (FEI) as part of an AiF (Arbeitsgemeinschaft industrieller Forschungsvereinigungen Otto von Guericke) project of the Industrielle Gemeinschaftsforschung (IGF)
- Thuringer Ministerium fur Bildung, Wissenschaft und Kultur
- Stiftung fur Technologie und Forschung
- Deutsche Forschungsgemeinschaft [RTG 1715, CRC 1278]
- German Federal Ministry of Education and Research (nutriCARD) [01EA1411A]
- Free State of Thuringia
- European Social Fund [2016 FGR 0045]
Objective: Myocardial infarction (MI) is a leading cause of mortality and morbidity worldwide and new treatment strategies are highly sought-after. Paradoxically, reperfusion of the ischemic myocardium, as achieved with early percutaneous intervention, results in substantial damage to the heart (ischemia/reperfusion injury) caused by cell death due to aggravated inflammatory and oxidative stress responses. Chronic therapy with vitamin E is not effective in reducing the cardiovascular event rate, presumably through failing to reduce atherosclerotic plaque instability. Notably, acute treatment with vitamin E in patients suffering a MI has not been systematically investigated. Methods and results: We applied alpha-tocopherol (alpha-TOH), the strongest anti-oxidant form of vitamin E, in murine cardiac ischemia/reperfusion injury induced by ligation of the left anterior descending coronary artery for 60 min. alpha-TOH significantly reduced infarct size, restored cardiac function as measured by ejection fraction, fractional shortening, cardiac output, and stroke volume, and prevented pathological changes as assessed by state-of-the-art strain and strain-rate analysis. Cardioprotective mechanisms identified, include a decreased infiltration of neutrophils into cardiac tissue and a systemic anti-inflammatory shift from Ly6C(high) to Ly6C(low) monocytes. Furthermore, we found a reduction in myeloperoxidase expression and activity, as well as a decrease in reactive oxygen species and the lipid peroxidation markers phosphatidylcholine (PC) (16:0)-9-hydroxyoctadecadienoic acid (HODE) and PC(16:0)-13-HODE) within the infarcted tissue. Conclusion: Overall, alpha-TOH inhibits ischemia/reperfusion injury-induced oxidative and inflammatory responses, and ultimately preserves cardiac function. Therefore, our study provides a strong incentive to test vitamin E as an acute therapy in patients suffering a MI.
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