Sivakumar Bhavana, Kurian Gino A
School of Chemical and Biotechnology, Vascular Biology lab, SASTRA Deemed University, Thanjavur, India.
School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, India.
Inhal Toxicol. 2022;34(5-6):107-119. doi: 10.1080/08958378.2022.2049931. Epub 2022 Mar 15.
Ambient exposure of PM from diesel exhaust (termed as diesel particulate matter [DPM]) can induce cardiotoxicity that can be manifested into myocardial ischemia/infarction, where the survival depends on mitochondrial function. The mechanism for DPM-induced mitochondrial dysfunction is yet to be elucidated and the consequential impact of impaired mitochondria on the severity of myocardial infarction (MI) has not been established. Female Wistar rats were exposed to DPM (0.5 mg/ml) for 3 h daily (to achieve a PM concentration of 250 µg/m) for 21 d trailed by an induction of MI using isoproterenol (ISO). DPM exposure altered the basal ECG pattern and increased heart weight (HW) to body weight (BW) ratio from control. Loss of mitochondrial quality in the cardiac tissue was observed in DPM exposed animals, measured declined ETC enzyme activity, reduced ATP levels, high oxidative stress, low mitochondrial copy number, and low expression of the mitochondrial genes involved in mitophagy (PINK and PARKIN) and mitochondrial fusion (MFN-1). Subsequent induction of MI in DPM exposed animals (DPM + ISO) further deteriorated the normal sinus rhythm, accompanied by elevated plasma CK and LDH level, increased myocardial caspase activity, downregulation of Peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α), transcription factor A (TFAM), DNA polymerase subunit gamma (POLG), and other mitochondrial quality control genes. Based on these results, we conclude that DPM alters the electrophysiology and ultrastructure of the heart that aggravates the MI-induced cardiotoxicity, where the diminished mitochondrial quality can be the potential contributor.
环境暴露于来自柴油废气的颗粒物（称为柴油颗粒物[DPM]）可诱发心脏毒性，表现为心肌缺血/梗死，其存活取决于线粒体功能。DPM诱导的线粒体功能障碍机制尚待阐明，线粒体受损对心肌梗死（MI）严重程度的后续影响也未明确。将雌性Wistar大鼠每天暴露于DPM（0.5mg/ml）3小时（以达到250μg/m的颗粒物浓度），持续21天，随后使用异丙肾上腺素（ISO）诱导MI。DPM暴露改变了基础心电图模式，与对照组相比，心脏重量（HW）与体重（BW）之比增加。在暴露于DPM的动物中观察到心脏组织中线粒体质量下降，表现为ETC酶活性降低、ATP水平降低、高氧化应激、线粒体拷贝数低以及参与线粒体自噬（PINK和PARKIN）和线粒体融合（MFN-1）的线粒体基因表达低。随后在暴露于DPM的动物（DPM+ISO）中诱导MI，进一步使正常窦性心律恶化，伴有血浆CK和LDH水平升高、心肌半胱天冬酶活性增加、过氧化物酶体增殖物激活受体γ共激活因子（PGC1-α）、转录因子A（TFAM）、DNA聚合酶亚基γ（POLG）和其他线粒体质量控制基因的下调。基于这些结果，我们得出结论，DPM改变了心脏的电生理和超微结构，加重了MI诱导的心脏毒性，其中线粒体质量下降可能是潜在因素。
