cProtective Effects and Bioinformatic Analysis of Narciclasine on Vascular Aging via Cross-talk between Inflammation and Metabolism through Inhibiting Skeletal Muscle-specific Ceramide Synthase 1.
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.
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.