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The Gene Expression Profile in Endothelial Cells Exposed to Mitomycin C

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Abstract—

The expression of genes involved in DNA repair (DDB1, ERCC4, ERCC5), leukocyte adhesion (VCAM1, ICAM1, SELE, SELP), endothelial mechanotransduction (KLF4), endothelial differentiation (PECAM1, CDH5, CD34, NOS3), endothelial-to-mesenchymal transition (SNAI1, SNAI2, TWIST1, GATA4, ZEB1, CDH2), and also coding scavenger-receptors (LOX1, SCARF1, CD36, LDLR, VLDR), antioxidant system (PXDN, CAT, SOD1) and transcription factor (HEY2) has been studied using the quantitative PCR in primary human coronary (HCAEC) and internal thoracic (HITAEC) arteries endothelial cells exposed to alkylating mutagen mitomycin C (MMC). The study was carried out two time points after 6 h of incubation with MMC and after 6 h of the genotoxic load followed by 24 h of incubation in pure culture medium. After the exposure to MMC, a decreased expression of almost all studied genes was noted in the exposed HCAEC and HITAEC; the only exception was found in the case of SNAI2, which demonstrated a 4-fold increase in its expression compared to the unexposed control. Elimination of MMC from the both cell cultures was accompanied by increased expression of the VCAM1, ICAM1, SELE, SNAI2, KLF4 genes and decreased expression of the PECAM1, CDH5, CD34, ZEB1, CAT, PXDN genes. In addition, HITAEC cells were characterized by decreased expression of the SOD1, SCARF1, CD36 genes and an increased expression of the SNAI1 and TWIST1 genes; in HCAEC, increased expression of the LDLR and VLDLR genes was noted. Thus, the genotoxic stress, induced by the alkylating mutagen MMC, is associated with the endothelial dysfunction, manifested by the altered gene expression profile of the endothelial cell cultivated under conditions of the genotoxic load.

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Funding

This work was supported by a grant from the President of the Russian Federation for young scientists—candidates of science (PhD) МК-1228.2021.1.4.

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Authors and Affiliations

  1. Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy blvd. 6, 650002, Kemerovo, Russia

    M. Yu. Sinitsky, A. V. Tsepokina, A. G. Kutikhin, D. K. Shishkova & A. V. Ponasenko

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  1. M. Yu. Sinitsky
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  2. A. V. Tsepokina
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  3. A. G. Kutikhin
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  4. D. K. Shishkova
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  5. A. V. Ponasenko
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Correspondence to M. Yu. Sinitsky.

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Authors declare that they have no conflicts of interest. The work was not related to studies on humans or animals as the object, and was performed on commercially available cultures of primary endothelial cells.

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Translated by A. Medvedev

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Sinitsky, M.Y., Tsepokina, A.V., Kutikhin, A.G. et al. The Gene Expression Profile in Endothelial Cells Exposed to Mitomycin C. Biochem. Moscow Suppl. Ser. B 15, 255–261 (2021). https://doi.org/10.1134/S1990750821030100

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