ArticleCirculation research2021
SIRT6 Protects Smooth Muscle Cells From Senescence and Reduces Atherosclerosis.
Article in Circulation research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 147 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
147 citing papers in PubMed, 2 syntheses or guidelines pooled it, 224 citations in OpenAlex.
- Cardiovascular System is Influenced by Skeletal Muscle-derived Extracellular Vesicles, Myokines and MicroRNAs Based on Interorgan Communication: A Systematic Review.International journal of medical sciences · 2025Pooled it
- Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis.Cell reports · 2023Pooled it
- Predictors of long-term absence of coronary artery calcium in individuals with high blood pressure: results from the MESA study.Annals of medicine · 2023Trial
- Post‑translational modifications in atherosclerosis: Roles, mechanisms and therapeutic potential (Review).International journal of molecular medicine · 2026Review
- Design, Synthesis, and Biological Evaluation of Pyrazolyl Thioureas (PTUs) as SIRT1 and SIRT2 Inhibitors.ChemMedChem · 2026Article
- Salvianolic Acid a Disrupts the HSP90α-AKT-PERK Ternary Complex to Alleviate Atherosclerosis by Activating Endoplasmic Reticulum Stress of Senescent Vascular Smooth Muscle Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Subcellular sirtuin signaling networks: pivotal regulators of cardiovascular homeostasis and remodeling.Journal of molecular histology · 2026Review
- USP5 Stabilizes TGFBR1 to Drive Vascular Smooth Muscle Cell Senescence and Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inflammation in atherosclerosis: Drivers, mechanisms and therapies.Acta pharmaceutica Sinica. B · 2026Review
- Vascular Smooth Muscle Cell Plasticity in Atherosclerosis: Mechanisms, Recent Advances, and Therapeutic Implications.Reviews in cardiovascular medicine · 2026Review
- Epigenetic dynamics of cellular senescence: From mechanistic insights to precision senotherapy.Chinese medical journal · 2026Review
- SIRT6 alleviates ischemic injury via orchestrating the RREB1/Snail and STC1/Smad7 signaling pathways to regulate endothelial-mesenchymal transition.Science China. Life sciences · 2026Article
- Epigenetic regulation in atherosclerosis and its therapeutic potential.Nature reviews. Cardiology · 2026Review
- USP11 alleviates pathological cardiac hypertrophy via stabilizing SIRT6.Cellular and molecular life sciences : CMLS · 2026Article
- Hypertriglyceridaemia and its multifaceted mechanisms driving atherosclerotic cardiovascular disease.Lipids in health and disease · 2026Review
- Mitochondrial homeostasis: the central hub governing the progression of atherosclerosis.Precision clinical medicine · 2026Review
- Sirtuins in Medicine: Multifaceted Roles in Physiological Processes and Cardiovascular Diseases.Biomolecules · 2026Review
- PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification.Circulation · 2026Article
- The role of caveolin-1 in atherosclerosis and its molecular mechanism.Lipids in health and disease · 2026Review
- Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
87 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleVascular smooth muscle cell (VSMC) senescence promotes atherosclerosis and features of plaque instability, in part, through lipid-mediated oxidative DNA damage and telomere dysfunction. SIRT6 (Sirtuin 6) is a nuclear deacetylase involved in DNA damage response signaling, inflammation, and metabolism; however, its role in regulating VSMC senescence and atherosclerosis is unclear.
objectiveWe examined SIRT6 expression in human VSMCs, the role, regulation, and downstream pathways activated by SIRT6, and how VSMC SIRT6 regulates atherogenesis. METHODS AND
resultsSIRT6 protein, but not mRNA, expression was markedly reduced in VSMCs in human and mouse atherosclerotic plaques, and in human VSMCs derived from plaques or undergoing replicative or palmitate-induced senescence versus healthy aortic VSMCs. The ubiquitin ligase CHIP (C terminus of HSC70-interacting protein) promoted SIRT6 stability, but CHIP expression was reduced in human and mouse plaque VSMCs and by palmitate in a p38- and c-Jun N-terminal kinase-dependent manner. SIRT6 bound to telomeres, while SIRT6 inhibition using shRNA or a deacetylase-inactive mutant (SIRT6
conclusionsSIRT6 protein expression is reduced in human and mouse plaque VSMCs and is positively regulated by CHIP. SIRT6 regulates telomere maintenance and VSMC lifespan and inhibits atherogenesis, all dependent on its deacetylase activity. Our data show that endogenous SIRT6 deacetylase is an important and unrecognized inhibitor of VSMC senescence and atherosclerosis.
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Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.