Nanoparticles exposure: In-vitro and in-vivo investigation to evaluate cardiovascu1ar risk factors in normal and failing cardiac tissue [Esposizione a nanoparticelle: Studi in-vitro ed in-vivo per valutare i fattori di rischio cardiovascolari in cuori normali e patologici]

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 (TiO2) 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 tracheally-instilled 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 TiO2-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.