Mesoporous tantalum oxide nanomaterials induced cardiovascular endothelial cell apoptosis via mitochondrial-endoplasmic reticulum stress apoptotic pathway

Abstract

Along with its wide range of potential applications, human exposure to mesoporous tantalum oxide nanomaterials (PEG@mTa₂O₅) has substantially risen. Accumulative toxic investigations have shown the PEG@mTa₂O₅ intake and cardiovascular diseases (CVD). Endothelial cell death is crucial in the onset and development of atherosclerosis. Still, the molecular mechanism connecting PEG@mTa₂O₅ and endothelium apoptosis remains unclear. Herein, we studied the absorption and toxic action of mesoporous tantalum oxide (mTa₂O₅) nanomaterials with polyethylene glycol (PEG) utilizing human cardio microvascular endothelial cells (HCMECs). We also showed that PEG@mTa₂O₅ promoted apoptosis in endothelial cells using flow cytometry and AO-EB staining. In conjunction with the ultrastructure modifications, PEG@mTa₂O₅ prompted mitochondrial ROS production, cytosolic Ca²⁺ overload, ΔΨm collapse, and ER stress verified by elevated ER-Tracker staining, upregulated XBP1 and GRP78/BiP splicing. Remarkably, the systemic toxicity and blood compatibility profile of PEG@mTa₂O₅ can greatly improve successive therapeutic outcomes of NMs while reducing their adverse side effects. Overall, our findings suggested that PEG@mTa₂O₅-induced endothelium apoptosis was partially mediated by the activation of the endoplasmic reticulum stress-mitochondrial cascade.

Keywords:

• Tantalum oxide
• HCMECs
• apoptosis
• mitochondria
• endoplasmic reticulum
• animal model

Authors’ contributions

Yanyong Jiao, Xiwei Zhang, Hongyu Yang, Hao Ma – supported with synthesis, characterization, molecular and biochemical analysis, data curation, formal analysis, and validation. Junjie Zou – helped with supervised the research. The manuscript was written through the contributions of all authors. All authors have approved the final version of the manuscript.

Availability of data and materials

All data generated or analyzed during this study are included in this submitted article. The raw data shall be made available upon request to the corresponding author.

Consent for publication

All authors consent for publication.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics approval and consent to participate

Male BALB/C nude mice were housed in the Laboratory Animal Center of The First Affiliated Hospital with Nanjing Medical University (Jiangsu Province Hospital), Nanjing 210029, China. All the animal studies were conducted following the principles of the Institutional Animal Care and Use Committee.

Funding

The author(s) reported there is no funding associated with the work featured in this article.