Abstract 14724: Mitophagy in Ischemia/Reperfusion: Effects of High Fat Diet and Melatonin
Introduction: Mitophagy removes damaged mitochondria and prevents ROS overproduction and may be important in the outcome of myocardial ischemia/reperfusion (I/R). However little is known about mitophagy in myocardial I/R and its significance in obesity. The aims of this study were to evaluate in a rat model of the metabolic syndrome (i) effects of myocardial I/R on mitophagy, mitochondrial (mito) oxidative phosphorylation (ox phos) and infarct size (ii) the role of reactive oxygen species (ROS) in the above processes by pretreatment with melatonin, a powerful anti-oxidant.
Methods: Four groups of rats were studied namely, control ± melatonin (mel) (10mg/kg/day) and high fat diet (HFD) ± mel. After 16 weeks on the diet and mel treatment, hearts were perfused in the working mode and subjected to 20min global I and10 min (for Western blots) or 60 min R (for infarct size). Mito ox phos potential was measured polarographically with glutamate, malate and palmitoyl-carnitine as substrates. Expression of mito PINK1, p62/SQSTM1 (p62) and Parkin was studied by Western blot.
Results: HFD reduced infarct size after I/R compared to controls. Mel treatment caused a significant lowering in infarct size of both control and HFD rat hearts. With glutamate but not palmitoyl carnitine as substrate, QO2 (states 3 ,4) was significantly higher in HFD mito after I. Mel treatment for 16 weeks caused a significant reduction in QO2 (state 4) (substrate palmitoyl carnitine) in all groups. PINK1 and p62 expression was higher after I in control hearts compared to HFD. Mel lowered PINK1, p62 and PARKIN after I in control but not in HFD mito.
Conclusion: Cardioprotection in HFD hearts was associated with improvement in mito ox phos and reduced mitophagy. Melatonin improved QO2 (State 4) in all groups but was associated with a lowering in mitophagy in controls only, possibly as a result of its ROS scavenging effects.
Author Disclosures: A. Lochner: None. K. Dhanalaban: None. S.R. Mzezewa: None. B. Huisamen: None.
- © 2016 by American Heart Association, Inc.