CCL4 contributes to aging related angiogenic insufficiency through activating oxidative stress and endothelial inflammation

IF 9.2 1区医学 Q1 PERIPHERAL VASCULAR DISEASE Angiogenesis Pub Date : 2024-05-13 DOI:10.1007/s10456-024-09922-y

Ting-Ting Chang, Liang-Yu Lin, Ching Chen, Jaw-Wen Chen

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Abstract

Aging is a natural process associated with chronic inflammation in the development of vascular dysfunction. We hypothesized that chemokine C-C motif ligands 4 (CCL4) might play a vital role in aging-related vascular dysfunction. Circulating CCL4 was up-regulated in elderly subjects and in aged animals. CCL4 inhibition reduced generation of reactive oxygen species (ROS), attenuated inflammation, and restored cell functions in endothelial progenitor cells from elderly subjects and in aged human aortic endothelial cells. CCL4 promoted cell aging, with impaired cell functioning, by activating ROS production and inflammation. CCL4 knockout mice and therapeutic administration of anti-CCL4 neutralizing antibodies exhibited vascular and dermal anti-aging effects, with improved wound healing, via the down-regulation of inflammatory proteins and the activation of angiogenic proteins. Altogether, our findings suggested that CCL4 may contribute to aging-related vascular dysfunction via activating oxidative stress and endothelial inflammation. CCL4 may be a potential therapeutic target for vascular protections during aging.

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CCL4 通过激活氧化应激和内皮炎症，导致与衰老相关的血管生成不足。

衰老是一个自然过程，与血管功能障碍发展过程中的慢性炎症有关。我们假设趋化因子 C-C motif 配体 4（CCL4）可能在与衰老相关的血管功能障碍中扮演重要角色。在老年受试者和老年动物体内，循环中的 CCL4 上调。抑制 CCL4 可减少活性氧（ROS）的生成，减轻炎症反应，并恢复老年人内皮祖细胞和老年人类主动脉内皮细胞的细胞功能。CCL4 通过激活 ROS 的产生和炎症反应，促进细胞衰老，使细胞功能受损。通过下调炎症蛋白和激活血管生成蛋白，CCL4 基因敲除小鼠和治疗性服用抗 CCL4 中和抗体显示出血管和真皮抗衰老效果，并改善伤口愈合。总之，我们的研究结果表明，CCL4 可能通过激活氧化应激和内皮炎症，导致与衰老相关的血管功能障碍。CCL4可能是衰老过程中保护血管的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Angiogenesis PERIPHERAL VASCULAR DISEASE-

CiteScore

21.90

自引率

8.20%

发文量

审稿时长

6-12 weeks

期刊介绍： Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.