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Tetrahedral Boronate Ester as Regulators of Inflammation and Adhesion in ox-LDL Induced Atherosclerotic Model

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Abstract

Objective: Boron-based molecules have attracted the attention of researchers in recent years, as they have become one of the largest and fastest-growing research areas. Presented in this study, various effects of tetrahedral boronate ester (BE) on, VCAM-1, E-selectin, and MCP-1 gene, and protein expression in ox-LDL induced in vitro atherosclerotic model were determined. Methods: IC50 concentrations and effects of tetrahedral BE on cell survival were detected using XTT assay. Real-Time PCR (RT-PCR) was used to evaluate the mRNA expression levels of VCAM-1, E-selectin, MCP-1 genes and, western blotting determined the protein expression. Results: Tetrahedral BE compound did not show cytotoxicity against HUVECs at 50 µM concentration. ox-LDL treatment caused an increase in E-selectin, VCAM-1, and MCP-1 gene and protein expression levels in cell culture samples. Tetrahedral BE suppressed adhesion molecule expression such as VCAM-1 and E-selectin. Discussion: Tetrahedral BE treatment reversed all increases in E-selectin gene and protein expression levels in any of the treatment groups. ox-LDL increased VCAM-1 gene and protein expression, which was reversed by BE treatment in a dose-dependent manner. Moreover, ox-LDL triggered MCP-1 protein and gene expression levels and these increases were reversed significantly only by a mid and low-dose of BE treatment. The results showed that tetrahedral BE stabilized with N→B dative bond plays a protective role in the early stages of atherosclerosis. Conclusions: We reported a new tetrahedral boronate ester molecule based on trigonal-planar boronate ester and 4-hydroxy pyridine were designed and synthesized via B←N coordinate covalent bond. We have shown that boron-compound has decreased gene and protein expression of MCP-1, VCAM-1, and E-selectin increased by ox-LDL in the atherosclerosis model. These findings emerged that boron-based compounds could be an option for atherosclerosis treatment.

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DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the Harran University Research Fund (Grant no. 21273).

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Pharmacy, Harran University, 63290, Sanliurfa, Turkey

    U. Degirmenci & M. Yildirim

  2. Department of Chemistry, Arts and Science Faculty, Harran University, 63290, Sanliurfa, Turkey

    A. Kilic & R. Söylemez

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  1. U. Degirmenci
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Contributions

The authors UD and MY—designed the experiments and carried out cell culture and molecular experiments. The authors RS and AK—synthesized the samples and carried out their electrochemical study. The author AK—supervised the characterization studies and had an important contribution in writing the manuscript of the article. The authors UD and MY—participated in data processing and contributed to manuscript preparation.

All authors participated in the discussions.

Corresponding author

Correspondence to M. Yildirim.

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Informed consent was not required for this article. No conflict of interest was declared by the authors.

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Degirmenci, U., Kilic, A., Söylemez, R. et al. Tetrahedral Boronate Ester as Regulators of Inflammation and Adhesion in ox-LDL Induced Atherosclerotic Model. Russ J Bioorg Chem 50, 106–115 (2024). https://doi.org/10.1134/S1068162024010175

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