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Review
. 2014 Oct 26;6(10):1091-9.
doi: 10.4330/wjc.v6.i10.1091.

Mitochondria-targeted agents: Future perspectives of mitochondrial pharmaceutics in cardiovascular diseases

Thekkuttuparambil Ananthanarayanan Ajith  1 , Thankamani Gopinathan Jayakumar  1
Affiliations
Review

Mitochondria-targeted agents: Future perspectives of mitochondrial pharmaceutics in cardiovascular diseases

Thekkuttuparambil Ananthanarayanan Ajith et al. World J Cardiol. .

Abstract

Mitochondria are one of the major sites for the generation of reactive oxygen species (ROS) as an undesirable side product of oxidative energy metabolism. Damaged mitochondria can augment the generation of ROS. Dysfunction of mitochondria increase the risk for a large number of human diseases, including cardiovascular diseases (CVDs). Heart failure (HF) following ischemic heart disease, infantile cardiomyopathy and cardiac hypertrophy associated with left ventricular dilations are some of the CVDs in which the role of mitochondrial oxidative stress has been reported. Advances in mitochondrial research during the last decade focused on the preservation of its function in the myocardium, which is vital for the cellular energy production. Experimental and clinical trials have been conducted using mitochondria-targeted molecules like: MnSOD mimetics, such as EUK-8, EUK-134 and MitoSOD; choline esters of glutathione and N-acetyl-L-cysteine; triphenylphosphonium ligated vitamin E, lipoic acid, plastoquinone and mitoCoQ10; and Szeto-Schiller (SS)- peptides (SS-02 and SS-31). Although many results are inconclusive, some of the findings, especially on CoQ10, are worthwhile. This review summarizes the role of mitochondria-targeted delivery of agents and their consequences in the control of HF.

Keywords: Antioxidant; Cardiovascular diseases; Electron transport chain; Heart failure; Mitochondrial medicine; Oxidative stress.

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Figures

Figure 1
Figure 1
Formation of various reactive oxygen species in mitochondria. HO.: Hydroxyl radical; O2.-: Super oxide anion radical; ONOO-: Peroxynitrite; mtNOS: Mitochondrial-specific nitric oxide synthase; NO: Nitric oxide.
Figure 2
Figure 2
Factors that form and attenuate (antioxidants) reactive oxygen species in mitochondria. SDH: Succinate dehydrogenase; αKGDH: Alpha ketoglutarate dehydrogenase; MAO: Monoamine oxidase; Trx: Thioredoxins; Prx: Peroxiredoxin; OXPHOS: Oxidative phosphorylations; TNF-α: Tumor necrosis factor-alpha; GSH: Reduced glutathione; MnSOD: Manganese containing superoxide dismutase; GPx1: Glutathione peroxidase; CoQ10: Co-enzyme Q10.
Figure 3
Figure 3
Damage induced by reactive oxygen species in mitochondria. OXPHOS: Oxidative phosphorylations; ROS: Reactive oxygen species.
Figure 4
Figure 4
Crosstalk between mitochondrial Ca2+ handling and reactive oxygen species generation. PTP: Permeability transition pore; NOS: Nitric oxide synthase; ADP: Adenosine diphosphate; ATP: Adenosine triphosphate.
Figure 5
Figure 5
Myocardial infarction-induced mitochondrial damage and dysfunction that resulted in heart failure.
See this image and copyright information in PMC

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