Title:Targeting Mitochondria in Cardiovascular Diseases
Volume: 22
Issue: 37
Author(s): Filomena S.G. Silva, Rui F. Simoes, Renata Couto and Paulo J. Oliveira
Affiliation:
Keywords:
Ischaemia-reperfusion injury, heart mitochondria, mitochondria-targeted antioxidants, cardioprotective agents, oxidative stress,
calcium overload, mitochondrial permeability transition pore, mitochondrial biogenesis, drugs.
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.