Pterostilbene alleviates abdominal aortic aneurysm <i>via</i> inhibiting macrophage pyroptosis by activating the miR-146a-5p/TRAF6 axis

Cai, Huoying; Huang, Lin; Wang, Mingshan; Liu, Ruiming; Qiu, Jiacong; Qin, Yuansen; Yao, Xi; Wang, Shenming; Yao, Chen; Hu, Zuojun; Zhou, Yu

doi:10.1039/d3fo01235b

Cited by 3 publications

(1 citation statement)

References 66 publications

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“…In recent years, non-coding RNAs, especially lncRNAs and miRNAs, have been considered as gene expression regulators. A prior study reported that miR-146a-5P could inhibit macrophage pyroptosis and alleviate AAA [ 56 ]. Other studies reported that lncRNA FGD-AS1 could promote AAA occurrence by targeting miR-195-5P in vascular smooth muscle cells [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive transcriptomic analysis unveils macrophage-associated genes for establishing an abdominal aortic aneurysm diagnostic model and molecular therapeutic framework

Wu,

Yu,

Luo

et al. 2024

Eur J Med Res

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Background Abdominal aortic aneurysm (AAA) is a highly lethal cardiovascular disease. The aim of this research is to identify new biomarkers and therapeutic targets for the treatment of such deadly diseases. Methods Single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithms were used to identify distinct immune cell infiltration types between AAA and normal abdominal aortas. Single-cell RNA sequencing data were used to analyse the hallmark genes of AAA-associated macrophage cell subsets. Six macrophage-related hub genes were identified through weighted gene co-expression network analysis (WGCNA) and validated for expression in clinical samples and AAA mouse models. We screened potential therapeutic drugs for AAA through online Connectivity Map databases (CMap). A network-based approach was used to explore the relationships between the candidate genes and transcription factors (TFs), lncRNAs, and miRNAs. Additionally, we also identified hub genes that can effectively identify AAA and atherosclerosis (AS) through a variety of machine learning algorithms. Results We obtained six macrophage hub genes (IL-1B, CXCL1, SOCS3, SLC2A3, G0S2, and CCL3) that can effectively diagnose abdominal aortic aneurysm. The ROC curves and decision curve analysis (DCA) were combined to further confirm the good diagnostic efficacy of the hub genes. Further analysis revealed that the expression of the six hub genes mentioned above was significantly increased in AAA patients and mice. We also constructed TF regulatory networks and competing endogenous RNA networks (ceRNA) to reveal potential mechanisms of disease occurrence. We also obtained two key genes (ZNF652 and UBR5) through a variety of machine learning algorithms, which can effectively distinguish abdominal aortic aneurysm and atherosclerosis. Conclusion Our findings depict the molecular pharmaceutical network in AAA, providing new ideas for effective diagnosis and treatment of diseases.

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Section: Discussionmentioning

confidence: 99%

Comprehensive transcriptomic analysis unveils macrophage-associated genes for establishing an abdominal aortic aneurysm diagnostic model and molecular therapeutic framework

Wu,

Yu,

Luo

et al. 2024

Eur J Med Res

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Targeting the smooth muscle cell KEAP1-Nrf2-STING axis with pterostilbene attenuates abdominal aortic aneurysm

Zou,

Zheng,

et al. 2024

Phytomedicine

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Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis

Chen,

Wang,

Zhang

et al. 2024

Redox Biology

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Pterostilbene alleviates abdominal aortic aneurysm via inhibiting macrophage pyroptosis by activating the miR-146a-5p/TRAF6 axis

Abstract: Our findings provide evidence that macrophage pyroptosis contributes to the development of AAA and that the activation of the miR-146a/TRAF6 axis by pterostilbene protects against macrophage pyroptosis and AAA formation.

Cited by 3 publications

References 66 publications

Comprehensive transcriptomic analysis unveils macrophage-associated genes for establishing an abdominal aortic aneurysm diagnostic model and molecular therapeutic framework

Comprehensive transcriptomic analysis unveils macrophage-associated genes for establishing an abdominal aortic aneurysm diagnostic model and molecular therapeutic framework

Targeting the smooth muscle cell KEAP1-Nrf2-STING axis with pterostilbene attenuates abdominal aortic aneurysm

Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis

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