Department of Medicine and Surgery, University of Parma, Parma, Italy; CERT, Center of Excellence for Toxicological Research, University of Parma, Parma, Italy.
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
Environ Pollut. 2021 Sep 1;284:117163. doi: 10.1016/j.envpol.2021.117163. Epub 2021 Apr 20.
Air pollution is well recognized as a central player in cardiovascular disease. Exhaust particulate from diesel engines (DEP) is rich in nanoparticles and may contribute to the health effects of particulate matter in the environment. Moreover, diesel soot emitted by modern engines denotes defective surfaces alongside chemically-reactive sites increasing soot cytotoxicity. We recently demonstrated that engineered nanoparticles can cross the air/blood barrier and are capable to reach the heart. We hypothesize that DEP nanoparticles are pro-arrhythmogenic by direct interaction with cardiac cells. We evaluated the internalization kinetics and the effects of DEP, collected from Euro III (DEPe3, in the absence of Diesel Particulate Filter, DPF) and Euro IV (DEPe4, in the presence of DPF) engines, on alveolar and cardiac cell lines and on in situ rat hearts following DEP tracheal instillation. We observed significant differences in DEP size, metal and organic compositions derived from both engines. DEPe4 comprised ultrafine particles (<100 nm) and denoted a more pronounced toxicological outcome compared to DEPe3. In cardiomyocytes, particle internalization is fastened for DEPe4 compared to DEPe3. The in-vivo epicardial recording shows significant alteration of EGs parameters in both groups. However, the DEPe4-instilled group showed, compared to DEPe3, a significant increment of the effective refractory period, cardiac conduction velocity, and likelihood of arrhythmic events, with a significant increment of membrane lipid peroxidation but no increment in inflammation biomarkers. Our data suggest that DEPe4, possibly due to ultrafine nanoparticles, is rapidly internalized by cardiomyocytes resulting in an acute susceptibility to cardiac electrical disorder and arrhythmias that could accrue from cellular toxicity. Since the postulated transfer of nanoparticles from the lung to myocardial cells has not been investigated it remains open whether the effects on the cardiovascular function are the result of lung inflammatory reactions or due to particles that have reached the heart.
空气污染被公认为心血管疾病的主要诱因。柴油发动机排放的颗粒物（DEP）富含纳米颗粒，可能是环境中颗粒物对健康产生影响的原因之一。此外，现代发动机排放的柴油烟尘具有缺陷表面和化学活性部位，增加了烟尘的细胞毒性。我们最近的研究表明，工程纳米颗粒可以穿透气/血屏障，并到达心脏。我们假设 DEP 纳米颗粒通过与心脏细胞直接相互作用而具有致心律失常作用。我们评估了源自 Euro III（无柴油机颗粒过滤器，DEPe3）和 Euro IV（有柴油机颗粒过滤器，DEPe4）发动机的 DEP 纳米颗粒的内化动力学及其对肺泡和心肌细胞系的影响，并通过 DEP 气管内滴注研究了其对原位大鼠心脏的影响。我们观察到源自这两种发动机的 DEP 的尺寸、金属和有机成分存在显著差异。与 DEPe3 相比，DEPe4 包含更细小的颗粒（<100nm），并表现出更明显的毒性作用。在心肌细胞中，与 DEPe3 相比，DEPe4 的颗粒内化速度更快。在体内心外膜记录中，两组的 EG 参数均发生明显改变。然而，与 DEPe3 相比，DEPe4 滴注组的有效不应期、心脏传导速度和心律失常事件的发生概率显著增加，细胞膜脂质过氧化显著增加，而炎症生物标志物无显著增加。我们的数据表明，DEPe4 可能由于超细纳米颗粒而被心肌细胞快速内化，导致对心脏电紊乱和心律失常的急性易感性增加，这可能是由细胞毒性引起的。由于尚未研究纳米颗粒从肺部转移到心肌细胞的情况，因此心血管功能的这些影响是肺部炎症反应的结果，还是由于到达心脏的颗粒所致，目前尚不清楚。
