How inhaled nanoparticles contribute to vascular diseases

reference

Miller MR, Raftis JB, Langrish JP, et al. Inhaled nanoparticles accumulate in places of vascular diseases. acs-nano . 2017; 11 (5): 4542-4552.

objective

to determine whether inhaled nanoparticles directly cause cardiovascular disease (CVD) by moving over the lungs or simply triggering systemic inflammatory reactions.

draft

This paper reports on the results of a number of clinical and animal experiments, which are aimed at answering a specific question of how nanoparticles contribute to cardiovascular diseases. In each study, the participants were exposed to gold nanoparticles either by inhalation (humans) or direct instillation by the trachea (mice), followed by blood, urine or tissue samples.

participant

on the first (n = 14 men) and second (n = 19) study took healthy human voluntary part; Participants in the third human study were patients who had recently suffered a cardiovascular accident and for whom a carotid artery was planned (n = 12). The first experiment with rodents included normal mice; The second concerned Apolipoprotein-E-Knockout mice (Apoe-/-), which had been fed with a high-fat diet to accelerate the development of atherosclerotic lesions.

interventions

In all experiments, the participants were exposed to gold nanoparticles, but particle size and exposure duration varied. The participants of the first attempt at humans were exposed to an average of 3.8 nm particles for 2 hours; In the second study on humans, 10 small (~ 4 Nm) particles and 9 large (34 Nm) particles were exposed. In the first animal experiment, mice were exposed to different sizes from 2 to 200 Nm; In the second animal experiment, mice were exposed to 5 nm particles over 5 weeks. In the third human study, 3 of the 12 patients were suspended for 4 hours before the operation.

The knowledge from this study can help us to avert an increase in morbidity by promoting the implementation of secure manufacturing and handling practices to reduce accidental exposure.

gold nanoparticles were used because they have a size similar to that through combustion, but have a low biological activity; They are also easier to measure. Since the endogenous gold values ​​in the blood are low, the investigators were able to assume that any proven material was experimentally obtained.

target parameter

Concentrations of gold nanoparticles in blood, urine and carotid plaque fabric (animal experiment 2 and human experiment 3). The gold content was determined by means of high-resolution inductive inductive plasma mass spectroscopy (HR-ICPMS) and Raman microscopy.

results

gold was detected in the blood of healthy subjects, which were exposed to nanoparticles inhaled within 15 minutes, and was still available 3 months after the exposure. After inhalation of smaller (4–5 Nm) particles, the concentrations were significantly higher compared to larger (30+ Nm) particles. In the case of mice, the accumulation in the smaller (<10 nm) particles was significantly larger than in the larger (10–200 Nm) range.

Gold nanoparticles preferably in areas with stronger inflammation in both human and animal experiments, especially in vascular lesions. The authors conclude that inhaled gold nanoparticles quickly pass into the systemic cycle and accumulate in places of vascular inflammation. This provides a direct mechanism that explains the connection between environmentally related nanoparticles and cardiovascular diseases.

clinical implications

In recent years, various studies have reported significant relationships between the inhalative exposure to nanoparticles from vehicle gases and morbidity and mortality risk. We now have a decent explanation for why and how this happens. In addition, the rapid growth of the production and use of nanomaterials has the potential to significantly increase the exposure of humans. The knowledge from this study can help us to avert an increase in morbidity by promoting the implementation of secure manufacturing and handling practices in order to reduce accidental exposure. So far, our understanding of an action mechanism that would explain the association of cardiovascular diseases has been rudimentary. This paper promotes our understanding and certainly warns for caution.

The authors showed that inhaled nanoparticles in humans pass into the circulation in humans and the particles accumulate in places of vascular inflammation. The particle translocation seems to be dependent on size, with greater translocation and accumulation of smaller nanoparticles.

Earlier studies show that acute exposure to diesel exhaust gases in healthy people and in patients with coronary heart disease causes vascular dysfunction, thrombosis and myocardial ischemia. ^{1 The chronic exposure to particle -shaped air pollution is connected in both animals as well as in humans with the development and advancement of athherosclerosis brought. 2}

But it was not clear how this happened. It is known that inhaled particles are deposited deep in the lungs and trigger oxidative stress and inflammation. ^{3 states that the inflammatory mediators triggered by these particles come into the general cycle and influence the risk of illness. Others believe that the nanoparticles themselves penetrate the alveolar epithelium and get into the circulation and contribute directly to illnesses. 4 This paper suggests that the latter is more likely. It is probably not such an easy choice. In the end we will probably understand that the nanoparticles trigger tissue infections that increase the translocation of particles.}

While the results of this present study provide a convincing explanation for how the CVD risk can be related to the exposure to nanoparticles in the environment, it only indicates a possible explanation for that of Bakian et al Seestadt, ^{6 or the results of an observation study by Power et al., Which found a connection between air pollution and fear. These 2 publications indicate that nanoparticles not only get into the general cycle, but also pass the blood-brain barrier and also trigger mental illnesses.}

This study does not demonstrate a causal connection. The data only show that nanoparticles accumulate in places of vascular diseases; They do not prove that nanoparticles cause or aggravate CVD.

The results of this paper and similar studies should worry about our patients who suffer from CVD or for whom there is a risk. The limitation of exposure to the nanoparticles inhaled, in particular diesel exhaust gases, can help limit the progression of the disease. However, there are also less obvious sources of exposure to nanoparticles. The number of nanoparticles in our everyday environment continues to increase. For example, only a few toner ink that are used when printing at home and in the office would be recognized as dangers for CVD, but they free nanomaterials (which are used to improve the toner performance) and were associated with respiratory problems. ^{8 Also contain food dyes that get into the body and cause oxidative stress can. 9}

This paper expands our understanding of the problems caused by diesel and other by -products of the combustion of fossil fuels. The size and number of particles in the air can ultimately be of greater importance than the absolute mass, since smaller particles can represent a larger threat. This paper also draws us aware of the potential danger that assumes a variety of nanos substances that are considered benign, not because of their chemical components, but because of their size and ability to move and then accumulate at inflammatory spots.