Subchronic exposure to titanium dioxide nanoparticles modifies cardiac structure and performance in spontaneously hypertensive rats
Abstract Background 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 c...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-06-01
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| Series: | Particle and Fibre Toxicology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12989-019-0311-7 |
| _version_ | 1819051273584902144 |
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| author | Stefano Rossi Monia Savi Marta Mazzola Silvana Pinelli Rossella Alinovi Laura Gennaccaro Alessandra Pagliaro Viviana Meraviglia Maricla Galetti Omar Lozano-Garcia Alessandra Rossini Caterina Frati Angela Falco Federico Quaini Leonardo Bocchi Donatella Stilli Stéphane Lucas Matteo Goldoni Emilio Macchi Antonio Mutti Michele Miragoli |
| author_facet | Stefano Rossi Monia Savi Marta Mazzola Silvana Pinelli Rossella Alinovi Laura Gennaccaro Alessandra Pagliaro Viviana Meraviglia Maricla Galetti Omar Lozano-Garcia Alessandra Rossini Caterina Frati Angela Falco Federico Quaini Leonardo Bocchi Donatella Stilli Stéphane Lucas Matteo Goldoni Emilio Macchi Antonio Mutti Michele Miragoli |
| author_sort | Stefano Rossi |
| collection | DOAJ |
| description | Abstract Background 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. Results 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. Conclusions 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. |
| first_indexed | 2024-12-21T12:01:19Z |
| format | Article |
| id | doaj.art-ffd873d7d1bf46f0840221599f35a53f |
| institution | Directory Open Access Journal |
| issn | 1743-8977 |
| language | English |
| last_indexed | 2024-12-21T12:01:19Z |
| publishDate | 2019-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Particle and Fibre Toxicology |
| spelling | doaj.art-ffd873d7d1bf46f0840221599f35a53f2022-12-21T19:04:49ZengBMCParticle and Fibre Toxicology1743-89772019-06-0116111810.1186/s12989-019-0311-7Subchronic exposure to titanium dioxide nanoparticles modifies cardiac structure and performance in spontaneously hypertensive ratsStefano Rossi0Monia Savi1Marta Mazzola2Silvana Pinelli3Rossella Alinovi4Laura Gennaccaro5Alessandra Pagliaro6Viviana Meraviglia7Maricla Galetti8Omar Lozano-Garcia9Alessandra Rossini10Caterina Frati11Angela Falco12Federico Quaini13Leonardo Bocchi14Donatella Stilli15Stéphane Lucas16Matteo Goldoni17Emilio Macchi18Antonio Mutti19Michele Miragoli20Department of Medicine and Surgery, University of ParmaDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of ParmaDepartment of Medicine and Surgery, University of ParmaDepartment of Medicine and Surgery, University of ParmaDepartment of Medicine and Surgery, University of ParmaInstitute for Biomedicine, Eurac ResearchInstitute for Biomedicine, Eurac ResearchInstitute for Biomedicine, Eurac ResearchDepartment of Medicine and Surgery, University of ParmaNamur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences (NARILIS), Research Centre for the Physics of Matter and Radiation (PMR), University of NamurInstitute for Biomedicine, Eurac ResearchDepartment of Medicine and Surgery, University of ParmaDepartment of Medicine and Surgery, University of ParmaDepartment of Medicine and Surgery, University of ParmaDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of ParmaDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of ParmaNamur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences (NARILIS), Research Centre for the Physics of Matter and Radiation (PMR), University of NamurDepartment of Medicine and Surgery, University of ParmaCERT, Center of Excellence for Toxicological Research, INAIL, ex-ISPESL, University of ParmaDepartment of Medicine and Surgery, University of ParmaDepartment of Medicine and Surgery, University of ParmaAbstract Background 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s12989-019-0311-7Titanium dioxide nanoparticlesNanotoxicologyCardiac electrophysiologyCardiac fibrosisArrhythmias |
| spellingShingle | Stefano Rossi Monia Savi Marta Mazzola Silvana Pinelli Rossella Alinovi Laura Gennaccaro Alessandra Pagliaro Viviana Meraviglia Maricla Galetti Omar Lozano-Garcia Alessandra Rossini Caterina Frati Angela Falco Federico Quaini Leonardo Bocchi Donatella Stilli Stéphane Lucas Matteo Goldoni Emilio Macchi Antonio Mutti Michele Miragoli Subchronic exposure to titanium dioxide nanoparticles modifies cardiac structure and performance in spontaneously hypertensive rats Particle and Fibre Toxicology Titanium dioxide nanoparticles Nanotoxicology Cardiac electrophysiology Cardiac fibrosis Arrhythmias |
| title | Subchronic exposure to titanium dioxide nanoparticles modifies cardiac structure and performance in spontaneously hypertensive rats |
| title_full | Subchronic exposure to titanium dioxide nanoparticles modifies cardiac structure and performance in spontaneously hypertensive rats |
| title_fullStr | Subchronic exposure to titanium dioxide nanoparticles modifies cardiac structure and performance in spontaneously hypertensive rats |
| title_full_unstemmed | Subchronic exposure to titanium dioxide nanoparticles modifies cardiac structure and performance in spontaneously hypertensive rats |
| title_short | Subchronic exposure to titanium dioxide nanoparticles modifies cardiac structure and performance in spontaneously hypertensive rats |
| title_sort | subchronic exposure to titanium dioxide nanoparticles modifies cardiac structure and performance in spontaneously hypertensive rats |
| topic | Titanium dioxide nanoparticles Nanotoxicology Cardiac electrophysiology Cardiac fibrosis Arrhythmias |
| url | http://link.springer.com/article/10.1186/s12989-019-0311-7 |
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