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

Abstract

A previous study has reported that exposure to PM2.5 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 PM2.5 on IR associated mitochondrial dysfunction at the subpopulation level by administrating PM2.5 directly to isolated female rat hearts via KH buffer. Our results demonstrated that PM2.5 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 PM2.5 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.

PM2.5-Induced Cardiac Structural Modifications and Declined Pro-Survival Signalling Pathways Are Responsible for the Inefficiency of GSK-3β Inhibitor in Attenuating Myocardial Ischemia-Reperfusion Injury in Rats

“…Throughout the entire experiment, hemodynamic parameters were continuously monitored using AD instruments’ Lab chart software (LAB CHART PRO) from Australia. At the end of the experiment, the hearts were collected and preserved for subsequent analysis [ 16 ].…”

“…Furthermore, the interaction between PM 2.5 exposure and myocardial ischemia-reperfusion (IR) injury, a condition characterized by the temporary interruption and subsequent restoration of blood flow to the heart, presents an additional challenge [ 15 , 16 ]. IR injury is a significant contributor to myocardial damage, and understanding its pathophysiology is crucial to improving clinical outcomes [ 17 ].…”

“…IR injury is a significant contributor to myocardial damage, and understanding its pathophysiology is crucial to improving clinical outcomes [ 17 ]. PM 2.5 exposure, known to induce systemic inflammation and oxidative stress, has the potential to exacerbate myocardial injury following IR [ 15 , 16 ]. However, the underlying molecular mechanisms involved in the interplay between PM 2.5 exposure, IR injury, and the GSK3β signalling axis, as well as their impact on cardiac function and mitochondrial dysfunction, remain unclear.…”

Epigenetic mechanisms of particulate matter exposure: air pollution and hazards on human health

“…Since small particles of ≤10 µm are found in the air, it is believed that the only organ that can be damaged is the lung and therefore could only induce respiratory diseases. However, epidemiological studies have reported a relationship between PM 2.5 and the cardiovascular system resulting in hypertension, atherosclerosis, myocardial infarction, heart attacks, and alterations in heart rate ( Barr et al, 2012 ; Jacobs et al, 2012 ; Madrigano et al, 2013 ; Sivakumar et al, 2022 ; Mordukhovich et al, 2015 ; Kirrane et al, 2019 ; Hayes et al, 2020 ). Also, several studies reported the presence of electrocardiogram alterations such as ST-segment changes and T-wave amplitude alterations ( Chuang et al, 2008 ; Gardner et al, 2014 ).…”