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棕色脂肪组织衍生的 Nrg4 可减轻雄性小鼠的血管内皮炎症和动脉粥样硬化。

Brown adipose tissue-derived Nrg4 alleviates endothelial inflammation and atherosclerosis in male mice.

机构信息

Department of Endocrinology, General Hospital of Central Theater Command, Wuhan, China.

The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.

出版信息

Nat Metab. 2022 Nov;4(11):1573-1590. doi: 10.1038/s42255-022-00671-0. Epub 2022 Nov 18.

DOI:10.1038/s42255-022-00671-0
PMID:36400933
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9684073/
Abstract

Brown adipose tissue (BAT) activity contributes to cardiovascular health by its energy-dissipating capacity but how BAT modulates vascular function and atherosclerosis through endocrine mechanisms remains poorly understood. Here we show that BAT-derived neuregulin-4 (Nrg4) ameliorates atherosclerosis in mice. BAT-specific Nrg4 deficiency accelerates vascular inflammation and adhesion responses, endothelial dysfunction and apoptosis and atherosclerosis in male mice. BAT-specific Nrg4 restoration alleviates vascular inflammation and adhesion responses, attenuates leukocyte homing and reduces endothelial injury and atherosclerosis in male mice. In endothelial cells, Nrg4 decreases apoptosis, inflammation and adhesion responses induced by oxidized low-density lipoprotein. Mechanistically, protein kinase B (Akt)-nuclear factor-κB signaling is involved in the beneficial effects of Nrg4 on the endothelium. Taken together, the results reveal Nrg4 as a potential cross-talk factor between BAT and arteries that may serve as a target for atherosclerosis.

摘要

棕色脂肪组织（BAT）通过其能量消耗能力为心血管健康做出贡献，但 BAT 通过内分泌机制调节血管功能和动脉粥样硬化的机制仍知之甚少。本研究表明，BAT 衍生的神经调节蛋白 4（Nrg4）可改善小鼠的动脉粥样硬化。BAT 特异性 Nrg4 缺乏会加速雄性小鼠的血管炎症和黏附反应、内皮功能障碍和细胞凋亡以及动脉粥样硬化。BAT 特异性 Nrg4 恢复可减轻血管炎症和黏附反应，减少白细胞归巢，并减少内皮损伤和动脉粥样硬化。在血管内皮细胞中，Nrg4 可减少氧化型低密度脂蛋白诱导的细胞凋亡、炎症和黏附反应。在机制上，蛋白激酶 B（Akt）-核因子-κB 信号通路参与了 Nrg4 对血管内皮的有益作用。综上所述，这些结果揭示了 Nrg4 是 BAT 和动脉之间潜在的交流因子，可能成为动脉粥样硬化的治疗靶点。

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