Targeting Mitochondria in Cardiovascular Diseases

Curr Pharm Des. 2016;22(37):5698-5717. doi: 10.2174/1381612822666160822150243.

Abstract

Background: Cardiovascular diseases (CVDs) are one of the main factors responsible for human morbidity and mortality. Since mitochondria play a critical role in the regulation of cardiac tissue homeostasis, this organelle is a critical target for the protective effects of several pharmaceuticals. Although specific mitochondria-targeted antioxidants and some pharmacological agents are described as potential cardioprotective agents, there are still a few effective mitochondrial therapies for the treatment of CVDs. Agents which have potential cardioprotective effects by directly targeting mitochondria in vitro and in vivo are still in pre-clinical or clinical trials, hence their widespread use in the clinic is still far. Also, some of these agents have a decreased bioavailability or show some intrinsic toxicity, which also limits their working mitochondrial concentrations.

Methods: By initially using PubMed specific queries for literature search, we review here cardiac mitochondrial effects of specific targeted and non-targeted antioxidants and pharmacological agents, including MitoE, MitoQ, MitoSNO, Mito-TEMPOL, SkQ1, SkQR1, carvedilol, trimetazidine, ranolazine, diazoxide and propofol.

Results: The present review emphasizes new mitochondrial-targeting strategies which have emerged to address difficulties arising from current approaches. We also describe the strengths and weaknesses of these cardioprotective approaches.

Conclusion: Although effective therapies to target mitochondria in the context of CVDs are not under widespread clinical use, the new strategies proposed constitute a real promise for the development of therapies which may effectively prevent CVDs in the near future.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Cardiotonic Agents / chemistry
  • Cardiotonic Agents / pharmacology*
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / metabolism
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / metabolism

Substances

  • Antioxidants
  • Cardiotonic Agents