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Vascular toxicity of multi-walled carbon nanotubes targeting vascular endothelial growth factor
Xiao-Yu Dai1, Li-Jun Ren1, Lang Yan1
1Department of Health Toxicology, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China.
Abstract:
Multiwalled carbon nanotubes (MWCNTs) are currently widely used and are expected to be used as drug carriers and contrast agents in clinical practice. Previous studies mainly focused on their lung toxicity; therefore, their effects on the vascular endothelium are unclear. In this study, a human angiogenesis array was used to determine the effect of MWCNTs on the expression profile of angiogenic factors in endothelial cells and to clarify the role of vascular endothelial growth factor (VEGF) in MWCNT-induced endothelial cell injury at the cellular and animal levels. The results indicated that MWCNTs (20-30 nm and 30-50 nm) could enter endothelial cells and disrupt human umbilical vein endothelial cell (HUVECs) activity in a concentration-dependent manner. MWCNTs disrupted the tube formation ability and cell migration function of HUVECs. The results from a Matrigel Plug experiment in mice showed that angiogenesis in the MWCNT experimental group was significantly reduced. The results of a protein chip analysis indicated that VEGF expression in the MWCNT treatment group was decreased, a finding that was validated by ELISA results. The protein expression levels of AKT and eNOS in the MWCNT treatment group were significantly decreased; the administration of recombinant VEGF significantly alleviated the migration ability and tube formation ability of endothelial cells injured by MWCNTs, upregulated the protein expression of AKT and eNOS, and increased the number of neovascularization in mice in the MWCNT treatment group. This study demonstrated that MWCNTs affect angiogenesis via the VEGF-Akt-eNOS axis which can be rescued by VEGF endothelial treatment.
Insights
Multiwalled carbon nanotubes (MWCNTs) impair blood vessel formation by disrupting the VEGF-Akt-eNOS pathway in endothelial cells. This vascular damage can be reversed with vascular endothelial growth factor (VEGF) treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Vascular Biology
Background:
- Multiwalled carbon nanotubes (MWCNTs) are increasingly used in biomedical applications, including drug delivery.
- Previous research primarily focused on MWCNT lung toxicity, leaving their vascular effects largely unknown.
- Understanding MWCNT impact on vascular endothelium is crucial for safe clinical translation.
Purpose of the Study:
- To investigate the effects of MWCNTs on endothelial cells and angiogenesis.
- To elucidate the role of vascular endothelial growth factor (VEGF) in MWCNT-induced vascular injury.
- To explore the therapeutic potential of VEGF in mitigating MWCNT toxicity.
Main Methods:
- Human angiogenesis array to analyze angiogenic factor expression in endothelial cells.
- In vitro studies using human umbilical vein endothelial cells (HUVECs) to assess MWCNT effects on cell activity, migration, and tube formation.
- In vivo Matrigel Plug assay in mice to evaluate MWCNT impact on angiogenesis.
- Protein chip analysis and ELISA to measure VEGF, AKT, and eNOS expression.
- Administration of recombinant VEGF to assess its protective effects.
Main Results:
- MWCNTs entered endothelial cells and reduced HUVEC activity, migration, and tube formation in a dose-dependent manner.
- MWCNTs significantly inhibited angiogenesis in vivo and decreased VEGF, AKT, and eNOS protein expression.
- Recombinant VEGF treatment rescued endothelial cell function, restored AKT and eNOS levels, and promoted neovascularization in MWCNT-exposed mice.
Conclusions:
- MWCNTs induce vascular endothelial injury by interfering with the VEGF-Akt-eNOS signaling pathway.
- VEGF plays a critical role in mediating MWCNT-induced angiogenesis impairment.
- VEGF administration shows therapeutic promise for counteracting MWCNT-induced vascular toxicity.
