Genotoxic stress leads to the proinflammatory response of endothelial cells: an in vitro study

Sinitsky M.Y.1 , Sinitskaya A.V.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/PBMC20226805361      PubMed Id: 36373882
Year: 2022  Volume: 68  Issue: 5  Pages: 361-366
It was shown, that genotoxic stress can trigger endothelial disfunction and atherosclerosis, but the molecular genetic mechanisms of this process are poorly investigated. At the same time, inflammation also plays the important role in atherogenesis. This study aimed access of inflammatory marker expression in the endothelial cells exposed to alkylating mutagen mitomycin C (MMC). Primary human coronary (HCAEC) and internal thoracic artery endothelial cells (HITAEC) exposed to 500 ng/ml MMC (experimental group) and 0.9% NaCl (control) were used in this research. A gene expression profile was evaluated by quantitative reverse transcription PCR after 6 h exposure of endothelial cells to MMC (or 0.9% NaCl) followed by subsequent 24 h incubation in the mutagen-free cell growth media. The cytokine profile of endotheliocytes was studied by dot blotting. We found that MIF, IL-8, MCP-1, IP-10 and PDGFB were upregulated both in HCAEC and HITAEC, while MIP-1β release remained unchanged. TIMP-2 was upregulated in HCAEC but not in HITAEC. sTNF RI was expressed only in HCAEC. According to gene expression analysis, HCAEC exposed to MMC are characterized by the increased mRNA level of IL-8, MCP-1 and IP-10; decreased expression of TIMP-2 and no differences in the expression of MIF, MIP-1β and PDGFB compared to the control. In HITAEC, increased mRNA level of IL-8 and IP-10; decreased expression of MIF and TIMP-2, no differences in the expression of MCP-1, MIP-1β and PDGFB was shown. TNF-RI expression was not detected in both cell lines. Thus, genotoxic stress in endothelial cells induced by MMC leads to differential inflammatory response that can trigger endothelial dysfunction.
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Keywords: mutagenesis, genotoxic stress, atherogenesis, gene expression, cytokines, inflammation

Sinitsky, M. Y., Sinitskaya, A. V., Shishkova, D. K., Ponasenko, A. V. (2022). Genotoxic stress leads to the proinflammatory response of endothelial cells: an in vitro study. Biomeditsinskaya Khimiya, 68(5), 361-366.
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