Non-communicable diseases, intended as the results of a combination of inherited, environmental and biological factors, kill 40 million people each year, equivalent to roughly 70% of all premature deaths globally. The possibility that manufactured nanoparticles (NPs) may affect cardiac performance, has led to recognize NPs-exposure not only as a major Public Health concern, but also as an occupational hazard. In volunteers, NPs-exposure is problematic to quantify. We recently found that inhaled titanium dioxide NPs, one of the most produced engineered nanomaterials, acutely increased cardiac excitability and promoted arrhythmogenesis in normotensive rats by a direct interaction with cardiac cells. We hypothesized that such scenario can be exacerbated by latent cardiovascular disorders such as hypertension. We monitored cardiac electromechanical performance in spontaneously hypertensive rats (SHRs) exposed to titanium dioxide NPs for 6 weeks using a combination of cardiac functional measurements associated with toxicological, immunological, physical and genetic assays. Longitudinal radio-telemetry ECG recordings and multiple-lead epicardial potential mapping revealed that atrial activation times significantly increased as well as proneness to arrhythmia. At the third week of nanoparticles administration, the lung and cardiac tissue encountered a maladaptive irreversible structural remodelling starting with increased pro-inflammatory cytokines levels and lipid peroxidation, resulting in upregulation of the main pro-fibrotic cardiac genes. At the end of the exposure, the majority of spontaneous arrhythmic events terminated, while cardiac hemodynamic deteriorated and a significant accumulation of fibrotic tissue occurred as compared to control untreated SHRs. Titanium dioxide nanoparticles were quantified in the heart tissue although without definite accumulation as revealed by particle-induced X-ray emission and ultrastructural analysis. The co-morbidity of hypertension and inhaled nanoparticles induces irreversible hemodynamic impairment associated with cardiac structural damage potentially leading to heart failure. The time-dependence of exposure indicates a non-return point that needs to be taken into account in hypertensive subjects daily exposed to nanoparticles.

中文翻译：

---

慢性暴露于二氧化钛纳米颗粒可改变自发性高血压大鼠的心脏结构和性能

非传染性疾病是遗传，环境和生物因素共同作用的结果，每年造成4000万人死亡，约占全球所有过早死亡人数的70％。人造纳米颗粒（NPs）可能影响心脏功能的可能性已导致人们认识到NPs暴露不仅是主要的公共卫生问题，而且是职业危害。在志愿者中，NPs暴露难以量化。我们最近发现，通过与心肌细胞直接相互作用，吸入的二氧化钛NPs（一种生产量最高的工程化纳米材料）可显着提高心脏兴奋性并促进血压正常大鼠的心律失常。我们假设这种情况会因潜在的心血管疾病（例如高血压）而加剧。我们使用与毒理学，免疫学，物理和遗传学分析相关的心脏功能测量，监测了暴露于二氧化钛纳米颗粒6周的自发性高血压大鼠（SHRs）的心脏机电性能。纵向无线电遥测心电图记录和多导心外膜电势图显示，心房激活时间显着增加，并且容易出现心律不齐。在纳米颗粒给药的第三周，肺和心脏组织遇到适应不良的不可逆结构重塑，开始于促炎性细胞因子水平和脂质过氧化作用的增加，从而导致主要促纤维化心脏基因的上调。暴露结束后，大多数自发性心律失常事件终止，与对照组未治疗的SHRs相比，心脏的血液动力学恶化，并且纤维化组织大量积聚。二氧化钛纳米颗粒在心脏组织中定量，尽管没有明确的积累，这是由颗粒诱导的X射线发射和超微结构分析所揭示的。高血压和吸入纳米颗粒的合并症会引起与心脏结构损害相关的不可逆的血液动力学损害，从而可能导致心力衰竭。暴露的时间依赖性表明，在每天暴露于纳米颗粒的高血压受试者中，必须考虑非返回点。二氧化钛纳米颗粒在心脏组织中定量，尽管没有明确的积累，这是由颗粒诱导的X射线发射和超微结构分析所揭示的。高血压和吸入纳米颗粒的合并症会引起与心脏结构损害相关的不可逆的血液动力学损害，从而可能导致心力衰竭。暴露的时间依赖性表明，在每天暴露于纳米颗粒的高血压受试者中，必须考虑非返回点。二氧化钛纳米颗粒在心脏组织中定量，尽管没有明确的积累，这是由颗粒诱导的X射线发射和超微结构分析所揭示的。高血压和吸入纳米颗粒的合并症会引起与心脏结构损害相关的不可逆的血液动力学损害，从而可能导致心力衰竭。暴露的时间依赖性表明，在每天暴露于纳米颗粒的高血压受试者中，必须考虑非返回点。