Targeting mitochondrial dysfunction and oxidative stress in heart failure: Challenges and opportunities

Free Radic Biol Med. 2018 Dec:129:155-168. doi: 10.1016/j.freeradbiomed.2018.09.019. Epub 2018 Sep 15.

Abstract

Mitochondrial dysfunction characterized by impaired bioenergetics, oxidative stress and aldehydic load is a hallmark of heart failure. Recently, different research groups have provided evidence that selective activation of mitochondrial detoxifying systems that counteract excessive accumulation of ROS, RNS and reactive aldehydes is sufficient to stop cardiac degeneration upon chronic stress, such as heart failure. Therefore, pharmacological and non-pharmacological approaches targeting mitochondria detoxification may play a critical role in the prevention or treatment of heart failure. In this review we discuss the most recent findings on the central role of mitochondrial dysfunction, oxidative stress and aldehydic load in heart failure, highlighting the most recent preclinical and clinical studies using mitochondria-targeted molecules and exercise training as effective tools against heart failure.

Keywords: Aldehydes; Cardiovascular diseases; Exercise training; Mitochondria; Redox imbalance; Therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aldehydes / antagonists & inhibitors
  • Aldehydes / metabolism
  • Animals
  • Antioxidants / therapeutic use*
  • Biomimetic Materials / therapeutic use*
  • Cardiotonic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Energy Metabolism / drug effects
  • Exercise
  • Heart Failure / metabolism
  • Heart Failure / pathology
  • Heart Failure / therapy*
  • Humans
  • Malondialdehyde / antagonists & inhibitors
  • Malondialdehyde / metabolism
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism
  • Mitochondria, Heart / pathology
  • Oxidative Stress / drug effects
  • Reactive Nitrogen Species / antagonists & inhibitors
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / chemistry
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / therapeutic use

Substances

  • Aldehydes
  • Antioxidants
  • Cardiotonic Agents
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Ubiquinone
  • Malondialdehyde
  • Superoxide Dismutase
  • coenzyme Q10
  • 4-hydroxy-2-nonenal