α-Tocopherol preserves cardiac function by reducing oxidative stress and inflammation in ischemia/reperfusion injury
Maria Wallert,
Melanie Ziegler,
Xiaowei Wang,
Ana Maluenda,
Xiaoqiu Xu,
May Lin Yap,
Roman Witt,
Corey Giles,
Stefan Kluge,
Marcus Hortmann,
Jianxiang Zhang,
Peter Meikle,
Stefan Lorkowski,
Karlheinz Peter
Affiliations
Maria Wallert
Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
Melanie Ziegler
Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
Xiaowei Wang
Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia
Ana Maluenda
Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
Xiaoqiu Xu
Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing, 400038, China
May Lin Yap
Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Department of Clinical Pathology, The University of Melbourne, Melbourne, Australia
Roman Witt
Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
Corey Giles
Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
Stefan Kluge
Department of Nutritional Biochemistry and Physiology, Institute of Nutritional Sciences, Friedrich Schiller University, Jena, Germany; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany
Marcus Hortmann
Department for Cardiology and Angiology, University Heart Centre, Freiburg, Germany
Jianxiang Zhang
Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing, 400038, China
Peter Meikle
Department of Medicine, Monash University, Melbourne, Australia; Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
Stefan Lorkowski
Department of Nutritional Biochemistry and Physiology, Institute of Nutritional Sciences, Friedrich Schiller University, Jena, Germany; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany
Karlheinz Peter
Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia; Corresponding author. Atherothrombosis and Vascular Biology Baker Heart and Diabetes Institute, 75 Commercial Rd, Melbourne, 3004, Australia.
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 (α-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. α-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 Ly6Chigh to Ly6Clow 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, α-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. Keywords: Oxidative stress, Tocopherol, ROS-Sensitive nanoprobe, Myocardial infarction, Ischemia/reperfusion injury
