Consequential Impact of Particulate Matter Linked Inter-Fibrillar Mitochondrial Dysfunction in Rat Myocardium Subjected to Ischemia Reperfusion Injury

SIMPLE SUMMARY: Inhalation of particulate matter (PM(2.5)) is known to cause cardiac effects and exacerbate any pre-existing cardiac diseases. However, the severity of toxicity depends on how much PM(2.5) has reached the blood circulation and then finally the heart. The consequential impact of PM(2.5) on the heart depends on its potential to alter cardiac oxidative stress and mitochondrial function that in turn controls the contractile function of the heart. In fact, this effect is partly concentration dependent. In the present study, we demonstrated that blood borne PM(2.5) can inflict cardiac injury and compromise physiological response. Moreover, the results from our study show that cardiac tolerance to resist ischemia reperfusion injury (IR) is low in PM(2.5) administered rat hearts. Cellular level analysis of the data suggests that PM(2.5) gets deposited in the mitochondria which in turn increases the oxidative stress by disturbing redox couple and inducing mitochondrial dysfunction. In fact, the higher pathological changes occur with the direct entry of PM into the myocardium. ABSTRACT: A previous study has reported that exposure to PM(2.5) from diesel exhaust (diesel particulate matter (DPM)) for 21 days can deteriorate the cardiac recovery from myocardial ischemia reperfusion injury (IR), where the latter is facilitated by the efficiency of mitochondrial subpopulations. Many investigators have demonstrated that IR impact on cardiac mitochondrial subpopulations is distinct. In the present study, we decipher the role of PM(2.5) on IR associated mitochondrial dysfunction at the subpopulation level by administrating PM(2.5) directly to isolated female rat hearts via KH buffer. Our results demonstrated that PM(2.5) administered heart (PM_C) severely deteriorated ETC enzyme activity (NQR, SQR, QCR, and COX) and ATP level in both IFM and SSM from the normal control. Comparatively, the declined activity was prominent in IFM fraction. Moreover, in the presence of IR (PM_IR), mitochondrial oxidative stress was higher in both subpopulations from the normal, where the IFM fraction of mitochondria experienced elevated oxidative stress than SSM. Furthermore, we assessed the in vitro protein translation capacity of IFM and SSM and found a declined ability in both subpopulations where the inability of IFM was significant in both PM_C and PM_IR groups. In support of these results, the expression of mitochondrial genes involved in fission, fusion, and mitophagy events along with the DNA maintenance genes such as GUF1, LRPPRC, and HSD17-b10 were significantly altered from the control. Based on the above results, we conclude that PM(2.5) administration to the heart inflicted mitochondrial damage especially to the IFM fraction, that not only deteriorated the cardiac physiology but also reduced its ability to resist IR injury.