Epigallocatechin gallate (EGCG) modulates senescent endothelial cell-monocyte communication in age-related vascular inflammation
Aging significantly affects intercellular communication between vascular endothelial cells (ECs) and hematopoietic cells, leading to vascular inflammation and age-associated diseases. This study determined how senescent ECs communicate with monocytes, whether extracellular vesicles (EVs) released fr...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2024.1506360/full |
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| author | Sarvatit Patel Kai Ellis Kai Ellis Corey A. Scipione Jason E. Fish Jason E. Fish Jason E. Fish Jason E. Fish Kathryn L. Howe Kathryn L. Howe Kathryn L. Howe Kathryn L. Howe Kathryn L. Howe |
| author_facet | Sarvatit Patel Kai Ellis Kai Ellis Corey A. Scipione Jason E. Fish Jason E. Fish Jason E. Fish Jason E. Fish Kathryn L. Howe Kathryn L. Howe Kathryn L. Howe Kathryn L. Howe Kathryn L. Howe |
| author_sort | Sarvatit Patel |
| collection | DOAJ |
| description | Aging significantly affects intercellular communication between vascular endothelial cells (ECs) and hematopoietic cells, leading to vascular inflammation and age-associated diseases. This study determined how senescent ECs communicate with monocytes, whether extracellular vesicles (EVs) released from senescent ECs affect monocyte functions, and investigated the potential for epigallocatechin-3-gallate (EGCG), a flavonoid in green tea, to reverse these effects. Human umbilical vein endothelial cells (HUVECs) were treated with Etoposide (10 µM, 24 h) to induce senescence, followed by EGCG (100 µM, 24 h) treatment to evaluate its potential as a senotherapeutic agent. The interaction between ECs and monocytes was analyzed using a co-culture system and direct treatment of monocytes with EC-derived EVs. EGCG reduced senescence-associated phenotypes in ECs, as evidenced by decreased senescence-associated (SA)-β-Gal activity and reversal of Etoposide-induced senescence markers. Monocytes co-cultured with EGCG-treated senescent ECs showed decreased pro-inflammatory responses compared to those co-cultured with untreated senescent ECs. Additionally, senescent ECs produced more EVs than non-senescent ECs. EVs from senescent ECs enhanced lipopolysaccharide (LPS)-induced pro-inflammatory activation of monocytes, whereas EVs from EGCG-treated senescent ECs mitigated this activation, maintaining monocyte activation at normal levels. Our findings reveal that EGCG confers anti-senescent effects via modulation of the senescent EC secretome (including EVs) with the capacity to modify monocyte activation. These findings suggest that EGCG could act as a senotherapeutic agent to reduce vascular inflammation related to aging. |
| format | Article |
| id | doaj-art-15e9ba18662a480a89f870a654c03f01 |
| institution | Kabale University |
| issn | 2297-055X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj-art-15e9ba18662a480a89f870a654c03f012025-01-21T08:37:04ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-01-011110.3389/fcvm.2024.15063601506360Epigallocatechin gallate (EGCG) modulates senescent endothelial cell-monocyte communication in age-related vascular inflammationSarvatit Patel0Kai Ellis1Kai Ellis2Corey A. Scipione3Jason E. Fish4Jason E. Fish5Jason E. Fish6Jason E. Fish7Kathryn L. Howe8Kathryn L. Howe9Kathryn L. Howe10Kathryn L. Howe11Kathryn L. Howe12Toronto General Hospital Research Institute, University Health Network, Toronto, ON, CanadaDepartment of Molecular Genetics, University of Toronto, Toronto, ON, CanadaDepartment of Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, CanadaToronto General Hospital Research Institute, University Health Network, Toronto, ON, CanadaToronto General Hospital Research Institute, University Health Network, Toronto, ON, CanadaInstitute of Medical Science, University of Toronto, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaPeter Munk Cardiac Centre, University Health Network, Toronto, ON, CanadaToronto General Hospital Research Institute, University Health Network, Toronto, ON, CanadaInstitute of Medical Science, University of Toronto, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaPeter Munk Cardiac Centre, University Health Network, Toronto, ON, CanadaDivision of Vascular Surgery, Department of Surgery, University of Toronto, Toronto, ON, CanadaAging significantly affects intercellular communication between vascular endothelial cells (ECs) and hematopoietic cells, leading to vascular inflammation and age-associated diseases. This study determined how senescent ECs communicate with monocytes, whether extracellular vesicles (EVs) released from senescent ECs affect monocyte functions, and investigated the potential for epigallocatechin-3-gallate (EGCG), a flavonoid in green tea, to reverse these effects. Human umbilical vein endothelial cells (HUVECs) were treated with Etoposide (10 µM, 24 h) to induce senescence, followed by EGCG (100 µM, 24 h) treatment to evaluate its potential as a senotherapeutic agent. The interaction between ECs and monocytes was analyzed using a co-culture system and direct treatment of monocytes with EC-derived EVs. EGCG reduced senescence-associated phenotypes in ECs, as evidenced by decreased senescence-associated (SA)-β-Gal activity and reversal of Etoposide-induced senescence markers. Monocytes co-cultured with EGCG-treated senescent ECs showed decreased pro-inflammatory responses compared to those co-cultured with untreated senescent ECs. Additionally, senescent ECs produced more EVs than non-senescent ECs. EVs from senescent ECs enhanced lipopolysaccharide (LPS)-induced pro-inflammatory activation of monocytes, whereas EVs from EGCG-treated senescent ECs mitigated this activation, maintaining monocyte activation at normal levels. Our findings reveal that EGCG confers anti-senescent effects via modulation of the senescent EC secretome (including EVs) with the capacity to modify monocyte activation. These findings suggest that EGCG could act as a senotherapeutic agent to reduce vascular inflammation related to aging.https://www.frontiersin.org/articles/10.3389/fcvm.2024.1506360/fullagingcardiovascular diseaseendothelial senescenceendothelial-monocyte communicationextracellular vesiclesinflammation |
| spellingShingle | Sarvatit Patel Kai Ellis Kai Ellis Corey A. Scipione Jason E. Fish Jason E. Fish Jason E. Fish Jason E. Fish Kathryn L. Howe Kathryn L. Howe Kathryn L. Howe Kathryn L. Howe Kathryn L. Howe Epigallocatechin gallate (EGCG) modulates senescent endothelial cell-monocyte communication in age-related vascular inflammation Frontiers in Cardiovascular Medicine aging cardiovascular disease endothelial senescence endothelial-monocyte communication extracellular vesicles inflammation |
| title | Epigallocatechin gallate (EGCG) modulates senescent endothelial cell-monocyte communication in age-related vascular inflammation |
| title_full | Epigallocatechin gallate (EGCG) modulates senescent endothelial cell-monocyte communication in age-related vascular inflammation |
| title_fullStr | Epigallocatechin gallate (EGCG) modulates senescent endothelial cell-monocyte communication in age-related vascular inflammation |
| title_full_unstemmed | Epigallocatechin gallate (EGCG) modulates senescent endothelial cell-monocyte communication in age-related vascular inflammation |
| title_short | Epigallocatechin gallate (EGCG) modulates senescent endothelial cell-monocyte communication in age-related vascular inflammation |
| title_sort | epigallocatechin gallate egcg modulates senescent endothelial cell monocyte communication in age related vascular inflammation |
| topic | aging cardiovascular disease endothelial senescence endothelial-monocyte communication extracellular vesicles inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2024.1506360/full |
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