Review
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World J Cardiol. Oct 26, 2014; 6(10): 1091-1099
Published online Oct 26, 2014. doi: 10.4330/wjc.v6.i10.1091
Mitochondria-targeted agents: Future perspectives of mitochondrial pharmaceutics in cardiovascular diseases
Thekkuttuparambil Ananthanarayanan Ajith, Thankamani Gopinathan Jayakumar
Thekkuttuparambil Ananthanarayanan Ajith, Department of Biochemistry, Amala Institute of Medical Sciences, Thrissur 680 555, Kerala, India
Thankamani Gopinathan Jayakumar, Department of Interventional Cardiology, Amala Cardiac Centre, Thrissur 680 555, Kerala, India
Author contributions: Ajith TA contributed the text and was involved in designing, drafting, editing and revising the article; Jayakumar TG gave substantial contributions to the conception and revision of the article critically for important intellectual content; both authors approved the final version of the manuscript to be published.
Correspondence to: Thekkuttuparambil Ananthanarayanan Ajith, PhD, Professor, Department of Biochemistry, Amala Institute of Medical Sciences, Amala Nagar, Thrissur 680 555, Kerala, India. taajith@rediffmail.com
Telephone: +91-487-2304116 Fax: +91-487-2307969
Received: May 15, 2014
Revised: July 7, 2014
Accepted: August 27, 2014
Published online: October 26, 2014
Processing time: 173 Days and 17.5 Hours
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: Cardiovascular diseases; Oxidative stress; Antioxidant; Electron transport chain; Mitochondrial medicine; Heart failure

Core tip: Dysfunction of mitochondria increases the risk for a large number of human diseases, including cardiovascular diseases. Heart failure (HF) following ischemic heart disease, infantile cardiomyopathy and cardiac hypertrophy associated with left ventricular dilations are some of the cardiovascular diseases in which the role of mitochondrial oxidative stress has been reported. Recent reports on chronic HF followed by ischemic heart disease suggested a reduced supply of energy necessary for the contractile function of cardiomyocytes. Since mitochondrial damages are central to the pathophysiology of HF, various approaches are used to target compounds at mitochondria alone or adjunct to standard therapies.