Protective effects and bioinformatic analysis of narciclasine on vascular aging via cross-talk between inflammation and metabolism through inhibiting skeletal muscle-specific ceramide synthase 1

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development Pub Date : 2025-02-01 DOI:10.1016/j.mad.2024.112021

Zhiyi Fang , Linghuan Wang , Yabin Wang , Yan Ma , Yan Fang , Weiwei Zhang , Ruihua Cao , Yingjie Zhang , Hui Li , Sijia Chen , Lei Tian , Xiaoying Shen , Feng Cao

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引用次数: 0

Abstract

Objective

The senescence of smooth muscle is one of the independent risk factors in atherosclerosis progression in which the vascular inflammation plays an important role on vascular dysfunction. This study is designed to explore the novel vascular aging biomarkers and screen the potential molecular interventional targets through bioinformatic analysis.

Results

Transcriptional analysis was conducted based on the GSE16487 open access database, which included 15 human vascular tissue samples from two groups: young group (≤ 60 years old, n = 8) and aged group (≥ 75 years old, n = 7). There were 275 differential expression genes (119 upregulated and 156 downregulated genes) with minimum 1.5-fold change between two groups. 9 genes were mainly participated in inflammation-related signaling pathways, in which narciclasine was validated as the most effective candidate for modulation the ceramide synthesis. In vitro and animal study demonstrated that narciclasine reversed vascular aging by inhibiting skeletal muscle-specific ceramide synthase 1 (CerS1), reducing the ceramide level derived from CerS1, and improving fat deposition and circulating glycolipid metabolism.

Conclusion

Narciclasine attenuates vascular aging and modulates the cross-talk between inflammation and metabolism via inhibiting skeletal muscle-specific ceramide synthase 1.

查看原文本刊更多论文

水仙素通过抑制骨骼肌特异性神经酰胺合成酶1在炎症与代谢间的交互作用对血管衰老的保护作用及生物信息学分析

目的：平滑肌衰老是动脉粥样硬化进展的独立危险因素之一，其中血管炎症在血管功能障碍中起重要作用。本研究旨在通过生物信息学分析，探索新的血管老化生物标志物，筛选潜在的分子干预靶点。结果：基于GSE16487开放获取数据库进行转录分析，共纳入青年组（≤60岁，n = 8）和老年组（≥75岁，n = 7）两组15份人血管组织样本，差异表达基因275个（上调119个，下调156个），两组差异表达基因差异最小1.5倍。9个基因主要参与炎症相关的信号通路，其中水仙素被证实是调节神经酰胺合成最有效的候选基因。体外和动物实验表明，水仙素通过抑制骨骼肌特异性神经酰胺合成酶1 （CerS1）、降低CerS1衍生的神经酰胺水平、改善脂肪沉积和循环糖脂代谢来逆转血管衰老。结论：水仙素通过抑制骨骼肌特异性神经酰胺合酶1，减缓血管衰老，调节炎症与代谢的交互作用。

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来源期刊

Mechanisms of Ageing and Development 医学-老年医学

CiteScore

11.10

自引率

1.90%

发文量

审稿时长

32 days

期刊介绍： Mechanisms of Ageing and Development is a multidisciplinary journal aimed at revealing the molecular, biochemical and biological mechanisms that underlie the processes of aging and development in various species as well as of age-associated diseases. Emphasis is placed on investigations that delineate the contribution of macromolecular damage and cytotoxicity, genetic programs, epigenetics and genetic instability, mitochondrial function, alterations of metabolism and innovative anti-aging approaches. For all of the mentioned studies it is necessary to address the underlying mechanisms. Mechanisms of Ageing and Development publishes original research, review and mini-review articles. The journal also publishes Special Issues that focus on emerging research areas. Special issues may include all types of articles following peered review. Proposals should be sent directly to the Editor-in-Chief.