Disruption of COMMD1 accelerates diabetic atherosclerosis by promoting glycolysis.

IF 2.8 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Diabetes & Vascular Disease Research Pub Date : 2023-01-01 DOI:10.1177/14791641231159009

Lili Zhang, Lihua Li, Yalan Li, Han Jiang, Zhen Sun, Guangyao Zang, Yongjiang Qian, Chen Shao, Zhongqun Wang

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引用次数: 1

Abstract

Aims: Diabetes will lead to serious complications, of which atherosclerosis is the most dangerous. This study aimed to explore the mechanisms of diabetic atherosclerosis.

Methods: ApoE^-/- mice were fed with an high-fat diet diet and injected with streptozotocin to establish an in vivo diabetic atherosclerotic model. RAW 264.7 cells were treated with oxidized low-density lipoprotein particles (ox-LDL) and high glucose to produce an in vitro diabetic atherosclerotic model.

Results: In this study, we showed that diabetes promoted the progression of atherosclerosis in ApoE^-/- mice and that high glucose potentiates macrophage proinflammatory activation and foam cell formation. Mechanistically, Copper metabolism MURR1 domain-containing 1(COMMD1) deficiency increased proinflammatory activation and foam cell formation, characterized by increased glycolysis, and then accelerated the process of atherosclerosis. Furthermore, 2-Deoxy-D-glucose (2-DG) reversed this effect.

Conclusion: Taken together, we provided evidence that the lack of COMMD1 accelerates diabetic atherosclerosis via mediating the metabolic reprogramming of macrophages. Our study provides evidence of a protective role for COMMD1 and establishes COMMD1 as a potential therapeutic strategy in patients with diabetic atherosclerosis.

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COMMD1的破坏通过促进糖酵解加速糖尿病动脉粥样硬化。

目的:糖尿病会导致严重的并发症，其中动脉粥样硬化是最危险的。本研究旨在探讨糖尿病动脉粥样硬化的发生机制。方法:采用高脂饲料喂养ApoE-/-小鼠，并注射链脲佐菌素建立糖尿病动脉粥样硬化模型。用氧化低密度脂蛋白颗粒(ox-LDL)和高糖处理RAW 264.7细胞，建立体外糖尿病动脉粥样硬化模型。结果:在本研究中，我们发现糖尿病促进ApoE-/-小鼠动脉粥样硬化的进展，高糖增强巨噬细胞的促炎激活和泡沫细胞的形成。机制上，铜代谢MURR1结构域1(COMMD1)缺乏增加了促炎激活和泡沫细胞的形成，表现为糖酵解增加，从而加速动脉粥样硬化的进程。此外，2-脱氧- d -葡萄糖(2-DG)逆转了这种作用。结论:综上所述，我们提供的证据表明COMMD1的缺乏通过介导巨噬细胞的代谢重编程加速了糖尿病动脉粥样硬化。我们的研究提供了COMMD1保护作用的证据，并确立了COMMD1作为糖尿病动脉粥样硬化患者的潜在治疗策略。

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

Diabetes & Vascular Disease Research ENDOCRINOLOGY & METABOLISM-PERIPHERAL VASCULAR DISEASE

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Diabetes & Vascular Disease Research is the first international peer-reviewed journal to unite diabetes and vascular disease in a single title. The journal publishes original papers, research letters and reviews. This journal is a member of the Committee on Publication Ethics (COPE)