Short- and Long-Term Endothelial Inflammation Have Distinct Effects and Overlap with Signatures of Cellular Senescence
This study investigates the interplay between cellular senescence and inflammation in human umbilical vein endothelial cells (HUVECs). We employed RNA sequencing to analyze gene expression changes in HUVECs subjected to replicative- or radiation-stress-induced senescence, and we compared these profi...
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MDPI AG
2025-05-01
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| Online Access: | https://www.mdpi.com/2073-4409/14/11/806 |
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| author | Barbora Belakova José Basílio Manuel Campos-Medina Anna F. P. Sommer Adrianna Gielecińska Ulrike Resch Johannes A. Schmid |
| author_facet | Barbora Belakova José Basílio Manuel Campos-Medina Anna F. P. Sommer Adrianna Gielecińska Ulrike Resch Johannes A. Schmid |
| author_sort | Barbora Belakova |
| collection | DOAJ |
| description | This study investigates the interplay between cellular senescence and inflammation in human umbilical vein endothelial cells (HUVECs). We employed RNA sequencing to analyze gene expression changes in HUVECs subjected to replicative- or radiation-stress-induced senescence, and we compared these profiles with those of cells under acute or chronic TNFα-mediated inflammation. Our findings reveal that both senescence types exhibited significant upregulation of genes associated with epithelial- (or endothelial) mesenchymal transition (EMT) and inflammatory pathways, indicating a shared molecular response. Notably, chronic inflammation led to a pronounced EMT signature, while acute inflammation primarily activated classical inflammatory responses. Experimental validation confirmed reduced proliferation and increased secretion of pro-inflammatory cytokines (IL-6 and IL-8) in senescent and chronically inflamed cells and substantiated the upregulation of EMT marker genes. Additionally, we observed impaired wound healing capacity in senescent and chronically inflamed cells, highlighting the functional consequences of these cellular states. Our study underscores the critical role of inflammation in exacerbating senescence-related changes, contributing to the understanding of age-related cardiovascular pathologies. These insights may inform future therapeutic strategies aimed at mitigating the effects of aging and inflammation on endothelial function and cardiovascular health. |
| format | Article |
| id | doaj-art-60d57a1fe12e444cb5b52c2d63df39e3 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-60d57a1fe12e444cb5b52c2d63df39e32025-08-20T03:46:48ZengMDPI AGCells2073-44092025-05-01141180610.3390/cells14110806Short- and Long-Term Endothelial Inflammation Have Distinct Effects and Overlap with Signatures of Cellular SenescenceBarbora Belakova0José Basílio1Manuel Campos-Medina2Anna F. P. Sommer3Adrianna Gielecińska4Ulrike Resch5Johannes A. Schmid6Institute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, PolandInstitute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaThis study investigates the interplay between cellular senescence and inflammation in human umbilical vein endothelial cells (HUVECs). We employed RNA sequencing to analyze gene expression changes in HUVECs subjected to replicative- or radiation-stress-induced senescence, and we compared these profiles with those of cells under acute or chronic TNFα-mediated inflammation. Our findings reveal that both senescence types exhibited significant upregulation of genes associated with epithelial- (or endothelial) mesenchymal transition (EMT) and inflammatory pathways, indicating a shared molecular response. Notably, chronic inflammation led to a pronounced EMT signature, while acute inflammation primarily activated classical inflammatory responses. Experimental validation confirmed reduced proliferation and increased secretion of pro-inflammatory cytokines (IL-6 and IL-8) in senescent and chronically inflamed cells and substantiated the upregulation of EMT marker genes. Additionally, we observed impaired wound healing capacity in senescent and chronically inflamed cells, highlighting the functional consequences of these cellular states. Our study underscores the critical role of inflammation in exacerbating senescence-related changes, contributing to the understanding of age-related cardiovascular pathologies. These insights may inform future therapeutic strategies aimed at mitigating the effects of aging and inflammation on endothelial function and cardiovascular health.https://www.mdpi.com/2073-4409/14/11/806senescenceacute inflammationchronic inflammationtranscriptomicsgene set enrichment analysismolecular signatures |
| spellingShingle | Barbora Belakova José Basílio Manuel Campos-Medina Anna F. P. Sommer Adrianna Gielecińska Ulrike Resch Johannes A. Schmid Short- and Long-Term Endothelial Inflammation Have Distinct Effects and Overlap with Signatures of Cellular Senescence Cells senescence acute inflammation chronic inflammation transcriptomics gene set enrichment analysis molecular signatures |
| title | Short- and Long-Term Endothelial Inflammation Have Distinct Effects and Overlap with Signatures of Cellular Senescence |
| title_full | Short- and Long-Term Endothelial Inflammation Have Distinct Effects and Overlap with Signatures of Cellular Senescence |
| title_fullStr | Short- and Long-Term Endothelial Inflammation Have Distinct Effects and Overlap with Signatures of Cellular Senescence |
| title_full_unstemmed | Short- and Long-Term Endothelial Inflammation Have Distinct Effects and Overlap with Signatures of Cellular Senescence |
| title_short | Short- and Long-Term Endothelial Inflammation Have Distinct Effects and Overlap with Signatures of Cellular Senescence |
| title_sort | short and long term endothelial inflammation have distinct effects and overlap with signatures of cellular senescence |
| topic | senescence acute inflammation chronic inflammation transcriptomics gene set enrichment analysis molecular signatures |
| url | https://www.mdpi.com/2073-4409/14/11/806 |
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