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Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction - PubMed

  • ️Mon Jan 01 2024

Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction

Maxim Sinitsky et al. Int J Mol Sci. 2024.

Abstract

Mitomycin C (MMC)-induced genotoxic stress can be considered to be a novel trigger of endothelial dysfunction and atherosclerosis-a leading cause of cardiovascular morbidity and mortality worldwide. Given the increasing genotoxic load on the human organism, the decryption of the molecular pathways underlying genotoxic stress-induced endothelial dysfunction could improve our understanding of the role of genotoxic stress in atherogenesis. Here, we performed a proteomic profiling of human coronary artery endothelial cells (HCAECs) and human internal thoracic endothelial cells (HITAECs) in vitro that were exposed to MMC to identify the biochemical pathways and proteins underlying genotoxic stress-induced endothelial dysfunction. We denoted 198 and 71 unique, differentially expressed proteins (DEPs) in the MMC-treated HCAECs and HITAECs, respectively; only 4 DEPs were identified in both the HCAECs and HITAECs. In the MMC-treated HCAECs, 44.5% of the DEPs were upregulated and 55.5% of the DEPs were downregulated, while in HITAECs, these percentages were 72% and 28%, respectively. The denoted DEPs are involved in the processes of nucleotides and RNA metabolism, vesicle-mediated transport, post-translation protein modification, cell cycle control, the transport of small molecules, transcription and signal transduction. The obtained results could improve our understanding of the fundamental basis of atherogenesis and help in the justification of genotoxic stress as a risk factor for atherosclerosis.

Keywords: DNA damage; atherogenesis; bioinformatic analysis; differentially expressed proteins; endothelial disfunction; genotoxic stress; mass spectrometry; mutagenesis; proteome.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1

Volcano plot showing the distribution of proteins in the proteome of HCAECs (A) and HITAECs (B). Gray points—the proteins with a log2 fold change < 1 and an FDR-corrected p-value > 0.05; green points—the proteins with a log2 fold change > 1 and an FDR-corrected p-value > 0.05; blue points—the proteins with a log2 fold change < 1 and an FDR-corrected p-value < 0.05; red points—the proteins with a log2 fold change > 1 and an FDR-corrected p-value < 0.05 (DEPs).

Figure 2
Figure 2

A Venn diagram demonstrating the number of unique and common DEPs in the MMC-treated HCAECs and HITAECs.

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