TiO2 nanosheets promote the transformation of vascular smooth muscle cells into foam cells in vitro and in vivo through the up-regulation of nuclear factor kappa B subunit 2

Shuang Li; Dejian Yan; Chaobo Huang; Fei Yang; Yi Cao

doi:10.1016/j.jhazmat.2021.127704

TiO₂ nanosheets promote the transformation of vascular smooth muscle cells into foam cells in vitro and in vivo through the up-regulation of nuclear factor kappa B subunit 2

J Hazard Mater. 2022 Feb 15;424(Pt D):127704. doi: 10.1016/j.jhazmat.2021.127704. Epub 2021 Nov 7.

Authors

Shuang Li¹, Dejian Yan², Chaobo Huang³, Fei Yang⁴, Yi Cao⁵

Affiliations

¹ Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China; College of Chemical Engineering, Nanjing Forestry University (NFU), Nanjing 210037, China; Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, China.
² Institute of Advanced Materials, North China Electric Power University, Beijing 102206, China.
³ College of Chemical Engineering, Nanjing Forestry University (NFU), Nanjing 210037, China.
⁴ Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China.
⁵ Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China; Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, China. Electronic address: caoyi39@126.com.

PMID: 34799167
DOI: 10.1016/j.jhazmat.2021.127704

Abstract

Titanium dioxide (TiO₂) nanomaterials have been shown to promote atherosclerosis through endothelial dysfunction. This study investigated the toxicity of TiO₂ nanosheets (NSs) to vascular smooth muscle cells (VSMCs), one of the pivotal cells involved in all stages of atherosclerosis. Only a high concentration of TiO₂ NSs (128 μg/mL) modestly induced cytotoxicity by decreasing thiols. RNA-sequencing data revealed that 64 μg/mL TiO₂ NSs significantly down-regulated 94 genes and up-regulated 174 genes, respectively. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to SMC function and lipid metabolism were altered. TiO₂ NSs increased nuclear factor kappa B subunit 2 (NFKB2), which led to a decrease in VSMC marker actin alpha 2, smooth muscle (ACTA2). On the other hand, macrophage marker CD36 and fatty acid synthase (FASN) proteins were increased. Additionally, TiO₂ NSs induced inflammatory cytokines and lipid accumulation, and these effects were curtailed by NFKB inhibitor - triptolide. Furthermore, repeated TiO₂ NS injection (5 mg/kg BW, once a day for 5 continuous days) into ICR mice led to increased NFKB2, CD36 and FASN, with a decreased ACTA2. Our results suggested that TiO₂ NSs promoted the transformation of VSMCs into foam cells through the up-regulation of NFKB2.

Keywords: Lipid droplet biogenesis; Nuclear factor kappa B subunit 2 (NFKB2); TiO(2) nanosheets (NSs); Transcriptomics; Vascular smooth muscle cells (VSMCs).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Atherosclerosis*
Cells, Cultured
Foam Cells*
Mice
Mice, Inbred ICR
Muscle, Smooth, Vascular
NF-kappa B / genetics
NF-kappa B p52 Subunit
Titanium
Up-Regulation

Substances

NF-kappa B
NF-kappa B p52 Subunit
Nfkb2 protein, mouse
titanium dioxide
Titanium