Patel Sarvatit, Ellis Kai, Scipione Corey A, Fish Jason E, Howe Kathryn L
Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Front Cardiovasc Med. 2025 Jan 21;11:1506360. doi: 10.3389/fcvm.2024.1506360. eCollection 2024.
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.
衰老显著影响血管内皮细胞（ECs）与造血细胞之间的细胞间通讯，导致血管炎症和与年龄相关的疾病。本研究确定了衰老的内皮细胞如何与单核细胞通讯，衰老内皮细胞释放的细胞外囊泡（EVs）是否影响单核细胞功能，并研究了绿茶中的黄酮类化合物表没食子儿没食子酸酯（EGCG）逆转这些作用的潜力。用人脐静脉内皮细胞（HUVECs）用依托泊苷（10 μM，24小时）处理以诱导衰老，然后用EGCG（100 μM，24小时）处理以评估其作为衰老治疗剂的潜力。使用共培养系统和用内皮细胞衍生的细胞外囊泡直接处理单核细胞来分析内皮细胞与单核细胞之间的相互作用。EGCG降低了内皮细胞中与衰老相关的表型，衰老相关（SA）-β-半乳糖苷酶活性降低和依托泊苷诱导的衰老标志物的逆转证明了这一点。与未处理的衰老内皮细胞共培养的单核细胞相比，与EGCG处理的衰老内皮细胞共培养的单核细胞显示出促炎反应降低。此外，衰老内皮细胞比非衰老内皮细胞产生更多的细胞外囊泡。来自衰老内皮细胞的细胞外囊泡增强了脂多糖（LPS）诱导的单核细胞促炎激活，而来自EGCG处理的衰老内皮细胞的细胞外囊泡减轻了这种激活，将单核细胞激活维持在正常水平。我们的研究结果表明，EGCG通过调节衰老内皮细胞分泌组（包括细胞外囊泡）赋予抗衰老作用，该分泌组具有改变单核细胞激活的能力。这些发现表明，EGCG可以作为一种衰老治疗剂来减少与衰老相关的血管炎症。
