2. Academic Validation
  3. Serum apolipoprotein A-I depletion is causative to silica nanoparticles-induced cardiovascular damage

Serum apolipoprotein A-I depletion is causative to silica nanoparticles-induced cardiovascular damage

  • Proc Natl Acad Sci U S A. 2021 Nov 2;118(44):e2108131118. doi: 10.1073/pnas.2108131118.
Xuting Liu 1 2,  Wei Wei 1,  Zixuan Liu 1,  Erqun Song 1,  Jianlin Lou 3,  Lingfang Feng 3,  Rongchong Huang 4,  Chunying Chen 5 6,  Pu Chun Ke 7 8,  Yang Song 9 2
Affiliations

Affiliations

  • 1 Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
  • 2 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
  • 3 School of Public Health, Hangzhou Medical College, Hangzhou 310051, China.
  • 4 Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100053, China.
  • 5 Chinese Academy of Sciences Center for Excellence in Nanoscience and Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China.
  • 6 Research Unit of Nanoscience and Technology, Chinese Academy of Medical Sciences, Beijing 100039, China.
  • 7 Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
  • 8 Nanomedicine Center, The Great Bay Area National Institute for Nanotechnology Innovation, Guangzhou 510700, China.
  • 9 Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China; yangsong@rcees.ac.cn.
PMID: 34716267 DOI: 10.1073/pnas.2108131118
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.

Keywords

apolipoprotein A-I; atherosclerosis; cardiovascular damage; corona; silica nanoparticle.

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