Mitochondria-targeted combination treatment strategy counteracts myocardial reperfusion injury of aged rats by modulating autophagy and inflammatory response

BackgroundAging, as a recognized risk factor for ischemic heart disease, interferes with protective mechanisms and abolishes the optimal effectiveness of cardioprotective interventions, leading to the loss of cardioprotection following myocardial ischemia/reperfusion (I/R) injury. This study was designed to explore the possible interaction of aging with cardioprotection induced by combination therapy with coenzyme Q(10) (CoQ(10)) and mitochondrial transplantation in myocardial I/R injury of aged rats.MethodsMale Wistar rats (n = 72, 400-450 g, 22-24 months old) were randomized into groups with/without I/R and/or CoQ(10) and mitochondrial transplantation, alone or in a combinational mode. An in vivo model of myocardial I/R injury was established by left anterior descending coronary artery occlusion and re-opening. Mitochondria were isolated from donor rats and injected intramyocardially (150 mu l of the mitochondrial suspension containing 2 x 10(5)+/- 0.3 x 10(5) mitochondria) at the onset of reperfusion in recipient groups. CoQ(10) (20 mg/kg/day) was injected intramuscularly for 7 days before I/R operation. Lastly, myocardial function, cTn-I level, expression of autophagy-associated proteins (Beclin1, p62, and LC3-II/LC3-I), and the levels of pro-inflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6) were assessed.ResultsCo-application of CoQ(10) and mitotherapy concomitantly improved myocardial function and decreased cTn-I level in aged reperfused hearts (P < .001). This combination therapy also modulated autophagic activity and decreased pro-inflammatory cytokines (P < .01 to P < .001). This combinational approach induced noticeable cardioprotection in comparison with monotherapies-received groups.ConclusionWe found that combination of CoQ(10) and mitochondrial transplantation attenuated myocardial I/R injury in aged rats, in part by modulating autophagy and inflammatory response, hence, appears to restore aging-related loss of cardioprotection in aged patients.

Automated summary

This study investigates the interaction between aging and cardioprotection induced by combination therapy with coenzyme Q(10) (CoQ(10)) and mitochondrial transplantation in myocardial ischemia/reperfusion (I/R) injury of aged rats. The results show that the combination of CoQ(10) and mitochondrial transplantation attenuates myocardial I/R injury in aged rats by modulating autophagy and inflammatory response, thereby restoring the aging-related loss of cardioprotection in aged patients.