[Exposure to nanoparticles: in vitro and in vivo studies to evaluate cardiovascular risk factors in normal and pathological cardiac tissues]

Nanoparticles toxicity is associated with cardiovascular diseases (CDs). Although epidemiological studies confirmed such link, they did not prove a direct causation on cardiac tissue. Normotensive and hypertensive (SHR) rats were exposed to titanium dioxide (TiO,) and diesel exhaust particles (DEP) from Euro3 and Euro4 derived-engines. We explored the interaction between NPs and in-vivo/in-vitro cardiac tissue and we determined the effect on electro-mechanical performance by evaluating genetic, morphological, functional and toxicological alterations. We observed a direct contamination of cardiac tissue by tracheallyinstilled NPs, correlated with structural remodeling, ROS, DNA damaged, modulation of ECGs and arrhythmogenesis. Such conditions are further aggravated in normotensive animal acutely exposed to Euro4-DEP and in SHR repeatedly exposed to 1i0,-NPs. Such NPs produce transient nanopores (≤50 nm), which causes membrane leakage and action potential reduction. Our proposed approaches show a direct involvement of NPs linked to CDs, by establishing a novel arrhythmogenic mechanism.