The gene expression signature in endothelial cells exposed to mitomycin C

Sinitsky M.Yu.1 , Tsepokina A.V.1, Kutikhin A.G.1, Shishkova D.K.1, Ponasenko A.V.1

1. Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20216702130      PubMed Id: 33860769
Year: 2021  Volume: 67  Issue: 2  Pages: 130-136
The expression of 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), scavenger receptors (LOX1, SCARF1, CD36, LDLR, VLDR), antioxidant system (PXDN, CAT, SOD1) and transcription factor (HEY2) genes in primary human coronary (HCAEC) and internal thoracic (HITAEC) arteries endothelial cells exposed to alkylating mutagen mitomycin C (MMC) was studied at 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 using the quantitative PCR. Immediately after MMC exposure, in the exposed HCAEC and HITAEC a decreased expression of almost all studied genes was noted excepted SNAI, which demonstrated a 4-told increase in its expression compared to the unexposed control. Elimination of MMC from the cultures, an increased expression of the VCAM1, ICAM1, SELE, SNAI2, KLF4 genes and a decreased the mRNA level of the PECAM1, CDH5, CD34, ZEB1, CAT, PXDN genes were observed in both cell lines. In addition, HITAEC cells were characterized by a decreased expression of the SOD1, SCARF1, CD36 genes and an increased expression of the SNAI1 and TWIST1 genes; in HCAEC, an increased mRNA level of the LDLR and VLDLR genes was noted. Thus, MMC-induced genotoxic stress is associated with the endothelial dysfunction.
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Keywords: mutagenesis, atherogenesis, endothelial dysfunction, gene expression

Sinitsky, M. Yu., Tsepokina, A. V., Kutikhin, A. G., Shishkova, D. K., Ponasenko, A. V. (2021). The gene expression signature in endothelial cells exposed to mitomycin C. Biomeditsinskaya Khimiya, 67(2), 130-136.
This paper is also available as the English translation: 10.1134/S1990750821030100
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