ArticleSignal transduction and targeted therapy2023
SIRT6 is an epigenetic repressor of thoracic aortic aneurysms via inhibiting inflammation and senescence.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Diosgenin presents a novel role in promoting diabetic wound healing: A mechanism involving Sirt6/Nrf2-mediated inhibition of ferroptosis.Journal of pharmaceutical analysis · 2026Article
- Review
- Deacetylation of SRF catalyzed by SIRT7 protects against abdominal aortic aneurysm formation.Experimental & molecular medicine · 2026Article
- SIRT6 enhances the therapeutic potential of extracellular vesicles in mitigating osteoarthritis in rat models.Stem cell research & therapy · 2026Article
- Targeting pyroptosis to treat aortic aneurysms: From mechanism to drug discovery (Review).International journal of molecular medicine · 2026Review
- Bioinformatics Identification and Molecular Docking Validation of Post-Translational Modification-Related Hub Genes as Diagnostic Biomarkers and Therapeutic Targets in Myocardial Fibrosis.International journal of molecular sciences · 2026Article
- NFS1 Regulates IDH2 to Attenuate Abdominal Aortic Aneurysms via Interacting With SP2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sirtuin 6 mitigates thoracic aortic aneurysm progression via maintenance of mitochondria homeostasis in vascular smooth muscle cells.Acta pharmacologica Sinica · 2026Article
- VSMCs and the immune microenvironment: a multidimensional regulatory network driving vascular injury and repair.Frontiers in immunology · 2026Review
- Mitochondrial dysfunction in aortic aneurysm and dissection: mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- Global Profiling of the Proteome and Acetylome in Mice with Abdominal Aortic Aneurysms.ACS omega · 2025Article
- Unraveling the meta-hallmarks between senescent and tumor cells: A new perspective for senolytic drug discovery.Acta pharmaceutica Sinica. B · 2025Review
- Cellular senescence in kidney diseases.Chinese medical journal · 2025Review
- Epigenetic Regulation of Aging and its Rejuvenation.MedComm · 2025Review
- Association of SIRT6 Expression With Risk of Pneumonitis Induced by Radiotherapy in Cancer Patients.Molecular carcinogenesis · 2025Article
- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
- Macrophage ILF3 promotes abdominal aortic aneurysm by inducing inflammatory imbalance in male mice.Nature communications · 2024Article
- Senescence in the bone marrow microenvironment: A driver in development of therapy-related myeloid neoplasms.Journal of bone oncology · 2024Article
- Smooth-Muscle-Cell-Specific Deletion of CD38 Protects Mice from AngII-Induced Abdominal Aortic Aneurysm through Inhibiting Vascular Remodeling.International journal of molecular sciences · 2024Article
- Metabolic mechanisms orchestrated by Sirtuin family to modulate inflammatory responses.Frontiers in immunology · 2024Review
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Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thoracic aortic aneurysms (TAAs) develop asymptomatically and are characterized by dilatation of the aorta. This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective treatments. The current understanding of the pathogenesis of TAA is still limited, especially for sporadic TAAs without known genetic mutation. Sirtuin 6 (SIRT6) expression was significantly decreased in the tunica media of sporadic human TAA tissues. Genetic knockout of Sirt6 in mouse vascular smooth muscle cells accelerated TAA formation and rupture, reduced survival, and increased vascular inflammation and senescence after angiotensin II infusion. Transcriptome analysis identified interleukin (IL)-1β as a pivotal target of SIRT6, and increased IL-1β levels correlated with vascular inflammation and senescence in human and mouse TAA samples. Chromatin immunoprecipitation revealed that SIRT6 bound to the Il1b promoter to repress expression partly by reducing the H3K9 and H3K56 acetylation. Genetic knockout of Il1b or pharmacological inhibition of IL-1β signaling with the receptor antagonist anakinra rescued Sirt6 deficiency mediated aggravation of vascular inflammation, senescence, TAA formation and survival in mice. The findings reveal that SIRT6 protects against TAA by epigenetically inhibiting vascular inflammation and senescence, providing insight into potential epigenetic strategies for TAA treatment.
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