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.
Keywords: Ischaemia-reperfusion injury, heart mitochondria, mitochondria-targeted antioxidants, cardioprotective agents, oxidative stress, calcium overload, mitochondrial permeability transition pore, mitochondrial biogenesis, drugs.