Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction
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 u...
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| Format: | Article |
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MDPI AG
2024-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/4044 |
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| author | Maxim Sinitsky Egor Repkin Anna Sinitskaya Victoria Markova Daria Shishkova Olga Barbarash |
| author_facet | Maxim Sinitsky Egor Repkin Anna Sinitskaya Victoria Markova Daria Shishkova Olga Barbarash |
| author_sort | Maxim Sinitsky |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T10:42:53Z |
| format | Article |
| id | doaj.art-fefaa823277a4dc2826772dcfa1a057e |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:42:53Z |
| publishDate | 2024-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fefaa823277a4dc2826772dcfa1a057e2024-04-12T13:20:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-04-01257404410.3390/ijms25074044Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial DysfunctionMaxim Sinitsky0Egor Repkin1Anna Sinitskaya2Victoria Markova3Daria Shishkova4Olga Barbarash5Laboratory of Genome Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Academician Barbarash Boulevard, 650002 Kemerovo, RussiaCentre for Molecular and Cell Technologies, St. Petersburg State University, 7/9 Universitetskaya Embankment, 199034 St. Petersburg, RussiaLaboratory of Genome Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Academician Barbarash Boulevard, 650002 Kemerovo, RussiaLaboratory for Molecular, Translation and Digital Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Academician Barbarash Boulevard, 650002 Kemerovo, RussiaLaboratory for Molecular, Translation and Digital Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Academician Barbarash Boulevard, 650002 Kemerovo, RussiaResearch Institute for Complex Issues of Cardiovascular Diseases, 6 Academician Barbarash Boulevard, 650002 Kemerovo, RussiaMitomycin 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.https://www.mdpi.com/1422-0067/25/7/4044mutagenesisatherogenesisendothelial disfunctiongenotoxic stressDNA damageproteome |
| spellingShingle | Maxim Sinitsky Egor Repkin Anna Sinitskaya Victoria Markova Daria Shishkova Olga Barbarash Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction International Journal of Molecular Sciences mutagenesis atherogenesis endothelial disfunction genotoxic stress DNA damage proteome |
| title | Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction |
| title_full | Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction |
| title_fullStr | Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction |
| title_full_unstemmed | Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction |
| title_short | Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction |
| title_sort | proteomic profiling of endothelial cells exposed to mitomycin c key proteins and pathways underlying genotoxic stress induced endothelial dysfunction |
| topic | mutagenesis atherogenesis endothelial disfunction genotoxic stress DNA damage proteome |
| url | https://www.mdpi.com/1422-0067/25/7/4044 |
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