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BRIEF RESEARCH REPORT article

Front. Cardiovasc. Med.
Sec. Heart Valve Disease
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1506360
This article is part of the Research Topic Investigating the Role of Extracellular Vesicles in Cardiovascular Disease Mechanisms View all 3 articles

Epigallocatechin Gallate (EGCG) Modulates Senescent Endothelial Cell-Monocyte Communication in Age-Related Vascular Inflammation

Provisionally accepted
Sarvatit Patel Sarvatit Patel 1Kai Ellis Kai Ellis 2,3Corey A Scipione Corey A Scipione 1Jason E. Fish Jason E. Fish 1,2Kathryn L Howe Kathryn L Howe 1,2*
  • 1 University Health Network (UHN), Toronto, Canada
  • 2 University of Toronto, Toronto, Ontario, Canada
  • 3 Sick Kids Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

The final, formatted version of the article will be published soon.

    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, 24h) to induce senescence, followed by EGCG (100 µM, 24h) 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 proinflammatory 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.

    Keywords: Aging, cardiovascular disease, Endothelial senescence, endothelial-monocyte communication, extracellular vesicles, Inflammation, Epigallocatechin gallate (EGCG)

    Received: 05 Oct 2024; Accepted: 26 Dec 2024.

    Copyright: © 2024 Patel, Ellis, Scipione, Fish and Howe. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Kathryn L Howe, University Health Network (UHN), Toronto, Canada

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.