Normandie Univ, UNIROUEN, UNICAEN, ABTE, 14000 Caen et 76 000 Rouen, France.
Normandie Univ, UNIROUEN, Institut National de la Santé et de la Recherche Médicale, U1096, Rouen, France.
Environ Pollut. 2019 Mar;246:518-526. doi: 10.1016/j.envpol.2018.12.049. Epub 2018 Dec 17.
Diesel exhaust (DE) contributes to air pollution, an important risk factor for cardiovascular diseases. However, the mechanisms by which DE exposure induces cardiovascular dysfunction remain unknown and there is still debate on the contribution of the primary particulate matter (PM) fraction compared to the gaseous phase. Although the mitochondria play a key role in the events leading to cardiovascular diseases, their role in DE-induced cardiovascular effects has not been investigated. The aim of this study was to highlight cardiac and mitochondrial events that could be disrupted following acute and/or repeated DE exposures and the contribution of gaseous pollutants to these effects. To address this question, Wistar rats were exposed to DE generated under strictly controlled and characterized conditions and extracted upstream or downstream of the diesel particulate filter (DPF). Evaluation of the cardiac function after acute DE exposure showed a disturbance in echocardiographic parameters, which persisted and worsened after repeated exposures. The presence of the DPF did not modify the cardiovascular dysfunction revealing an important implication of the gas phase in this response. Surprisingly, redox parameters were not altered by DE exposures while an alteration in mitochondrial oxidative capacity was observed. Exploration of the mitochondrial function demonstrated a more specific alteration in complex I of the respiratory chain after repeated exposures, which was further confirmed by transcriptional analysis of left ventricular (LV) tissue. In conclusion, this work provides new insights into cardiovascular effects induced by DE, demonstrating a cardiac mitochondrial impairment associated with the gaseous phase. These effects suggest deleterious consequences in terms of cardiac function for vulnerable populations with underlying energy deficit such as patients with heart failure or the elderly.
柴油机尾气（DE）造成了空气污染，这是心血管疾病的一个重要危险因素。然而，DE 暴露引起心血管功能障碍的机制尚不清楚，而且关于主要颗粒物（PM）部分与气相相比的贡献仍存在争议。尽管线粒体在导致心血管疾病的事件中起着关键作用，但它们在 DE 诱导的心血管效应中的作用尚未被研究。本研究的目的是强调心脏和线粒体事件，这些事件可能在急性和/或重复 DE 暴露后被打乱，以及气态污染物对这些效应的贡献。为了解决这个问题，Wistar 大鼠暴露于在严格控制和表征条件下产生的 DE，并在柴油机颗粒过滤器（DPF）的上游或下游提取 DE。急性 DE 暴露后心脏功能的评估显示，超声心动图参数发生了紊乱，这种紊乱在重复暴露后持续存在并恶化。DPF 的存在并没有改变心血管功能障碍，这表明气相在这种反应中具有重要的影响。令人惊讶的是，DE 暴露并没有改变氧化还原参数，而线粒体氧化能力的改变则被观察到。对线粒体功能的探索表明，重复暴露后呼吸链复合体 I 的功能出现了更特异的改变，这一发现通过对左心室（LV）组织的转录分析得到了进一步证实。总之，这项工作提供了对 DE 引起的心血管效应的新见解，证明了与气相有关的心脏线粒体损伤。这些效应表明，对于存在潜在能量缺陷的易受影响人群，如心力衰竭或老年人，心脏功能可能会产生有害后果。
