Elsevier

Redox Biology

Volume 26, September 2019, 101292
Redox Biology

Research Paper
α-Tocopherol preserves cardiac function by reducing oxidative stress and inflammation in ischemia/reperfusion injury

https://doi.org/10.1016/j.redox.2019.101292Get rights and content
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Highlights

  • α-TOH reduces cardiac I/R injury and preserves cardiac function in male C57BL/6 mice.

  • α-TOH reduces neutrophil and monocyte infiltration in the infarcted cardiac tissue.

  • Expression of inflammatory and oxidative markers is down-regulated by α-TOH.

  • α-TOH decreases the production of reactive oxygen species and peroxidized lipids.

Abstract

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

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1

These authors contributed equally.