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

Redox Biol. 2019 Sep:26:101292. doi: 10.1016/j.redox.2019.101292. Epub 2019 Aug 6.

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: Ischemia/reperfusion injury; Myocardial infarction; Oxidative stress; ROS-Sensitive nanoprobe; Tocopherol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cardiotonic Agents / metabolism*
  • Cardiotonic Agents / pharmacology
  • Cytokines / metabolism
  • Flow Cytometry
  • Gene Expression Profiling
  • Inflammation / drug therapy
  • Inflammation / etiology
  • Inflammation / metabolism*
  • Inflammation Mediators / metabolism
  • Lipid Metabolism / drug effects
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Myocardial Reperfusion Injury / drug therapy
  • Myocardial Reperfusion Injury / etiology
  • Myocardial Reperfusion Injury / metabolism*
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism*
  • Transcriptome
  • alpha-Tocopherol / metabolism*
  • alpha-Tocopherol / pharmacology

Substances

  • Biomarkers
  • Cardiotonic Agents
  • Cytokines
  • Inflammation Mediators
  • Reactive Oxygen Species
  • alpha-Tocopherol