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Serum apolipoprotein A-I depletion is causative to silica nanoparticles–induced cardiovascular damage
- Source :
- Proc Natl Acad Sci U S A
- Publication Year :
- 2021
- Publisher :
- Proceedings of the National Academy of Sciences, 2021.
-
Abstract
- The rapid development of nanotechnology has greatly benefited modern science and engineering and also led to an increased environmental exposure to nanoparticles (NPs). While recent research has established a correlation between the exposure of NPs and cardiovascular diseases, the intrinsic mechanisms of such a connection remain unclear. Inhaled NPs can penetrate the air-blood barrier from the lung to systemic circulation, thereby intruding the cardiovascular system and generating cardiotoxic effects. In this study, on-site cardiovascular damage was observed in mice upon respiratory exposure of silica nanoparticles (SiNPs), and the corresponding mechanism was investigated by focusing on the interaction of SiNPs and their encountered biomacromolecules en route. SiNPs were found to collect a significant amount of apolipoprotein A-I (Apo A-I) from the blood, in particular when the SiNPs were preadsorbed with pulmonary surfactants. While the adsorbed Apo A-I ameliorated the cytotoxic and proinflammatory effects of SiNPs, the protein was eliminated from the blood upon clearance of the NPs. However, supplementation of Apo A-I mimic peptide mitigated the atherosclerotic lesion induced by SiNPs. In addition, we found a further declined plasma Apo A-I level in clinical silicosis patients than coronary heart disease patients, suggesting clearance of SiNPs sequestered Apo A-I to compromise the coronal protein's regular biological functions. Together, this study has provided evidence that the protein corona of SiNPs acquired in the blood depletes Apo A-I, a biomarker for prediction of cardiovascular diseases, which gives rise to unexpected toxic effects of the nanoparticles.
- Subjects :
- Male
Apolipoprotein B
Protein Corona
Pharmacology
Cardiovascular System
Proinflammatory cytokine
Lesion
Mice
Silicosis
medicine
Animals
Nanotechnology
Particle Size
Respiratory system
Lung
Mice, Knockout
Multidisciplinary
Apolipoprotein A-I
biology
Chemistry
Environmental exposure
Biological Sciences
Silicon Dioxide
medicine.disease
Mice, Inbred C57BL
Oxidative Stress
medicine.anatomical_structure
Cardiovascular Diseases
biology.protein
Nanoparticles
Adsorption
medicine.symptom
Signal Transduction
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 118
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....286fcd8185f856012b6d8968d3c764ab