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Cardioprotective Effects of Selective Mitochondrial-Targeted Antioxidants in Myocardial Ischemia/Reperfusion (I/R) Injury
Research Day
  • Regina Ondrasik, Philadelphia College of Osteopathic Medicine
  • Qian Chen, Philadelphia College of Osteopathic Medicine
  • Katelyn Navitsky, Philadelphia College of Osteopathic Medicine
  • William Chau, Philadelphia College of Osteopathic Medicine
  • On Say Lau, Philadelphia College of Osteopathic Medicine
  • Issachar Devine, Philadelphia College of Osteopathic Medicine
  • Tyler Galbreath, Philadelphia College of Osteopathic Medicine
  • Robert J. Barsotti, Philadelphia College of Osteopathic Medicine
  • Lindon H. Young, Philadelphia College of Osteopathic Medicine
Location
Philadelphia Campus
Start Date
1-5-2013 2:00 PM
End Date
1-5-2013 4:00 PM
Disciplines
Description

During myocardial ischemia, coronary blood flow interruption deprives cardiomyocytes of oxygen, glucose and fatty acids. Ischemic damage is exacerbated by a burst of reactive oxygen species (ROS) generated at reperfusion when oxygen interacts with damaged mitochondrial electron transport chains (ETC), especially uncoupled complexes I and III (Fig. 1,2). Nicotinamide adenine dinucleotide phosphate oxidase (Nox) activity can also release ROS, inducing additional tissue/organ damage.

Surgical intervention or thrombolytic treatments can restore coronary blood flow. However, as blood flow reestablishes, oxidative stress leads to I/R injury. Clinical treatment remains a challenge as no pharmaceutical agents effectively limit I/R-induced damage. Mitochondria are implicated in I/R as a major source of ROS3,4,5. Excess ROS leads to mitochondrial and cardiac contractile dysfunction6. Conventional antioxidants have limited efficacy in myocardial I/R because they are not targeted selectively to where most I/R damage occurs, in mitochondria (Fig. 3)3,4,5. Mitoquinone (mitoQ, MW=600 g/mol), a coenzyme Q analog, easily crosses phospholipid bilayers and is driven by the large electrochemical membrane potential to concentrate mitoQ several hundred-fold within mitochondria. The respiratory chain reduces mitoQ to its active ubiquinol antioxidant form to limit myocardial I/R injury5. The SS-31 (Szeto-Schiller) peptide ((D-Arg)-Dmt-Lys-Phe-Amide, MW=640 g/mol, Genemed Synthesis, Inc., San Antonio, TX) is also of interest since it is cellpermeable, specifically targeted to inner mitochondrial membranes based on its alternating cationic aromatic residue sequence, with an antioxidant dimethyltyrosine moeity. SS peptides scavenge ROS in I/R models.

Although mitochondrial-targeted antioxidant pretreatment can effectively limit I/R injury, pretreatment is not always possible in cases of myocardial infarction. Therefore, evaluating cardioprotective efficacy of mitochondrialtargeted antioxidants when given at reperfusion is of high significance

Citation Information
Regina Ondrasik, Qian Chen, Katelyn Navitsky, William Chau, et al.. "Cardioprotective Effects of Selective Mitochondrial-Targeted Antioxidants in Myocardial Ischemia/Reperfusion (I/R) Injury" (2013)
Available at: http://works.bepress.com/qian_chen/6/