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The sirtuin family members SIRT1, SIRT3 and SIRT6: Their role in vascular biology and atherogenesis

  • Author Footnotes
    1 These authors contributed equally to this work.
    Bożena Sosnowska
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Hypertension, Medical University of Lodz, Lodz, Poland
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Mohsen Mazidi
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Key State Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
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  • Peter Penson
    Correspondence
    Corresponding author. School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK.
    Affiliations
    School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK
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  • Anna Gluba-Brzózka
    Affiliations
    Department of Nephrology, Hypertension and Family Medicine, WAM University Hospital, Lodz, Poland

    Polish Mother's Memorial Hospital Research Institute, Lodz, Poland
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  • Jacek Rysz
    Affiliations
    Department of Nephrology, Hypertension and Family Medicine, WAM University Hospital, Lodz, Poland
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  • Maciej Banach
    Correspondence
    Corresponding author. Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz, Poland.
    Affiliations
    Department of Hypertension, Medical University of Lodz, Lodz, Poland

    Polish Mother's Memorial Hospital Research Institute, Lodz, Poland

    Cardiovascular Research Centre, University of Zielona-Gora, Zielona-Gora, Poland
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  • Author Footnotes
    1 These authors contributed equally to this work.

      Highlights

      • The sirtuins (SIRTs) are a family of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases.
      • SIRTS have important roles in regulating energy metabolism and senescence.
      • Activation of SIRTs appears to have beneficial effects on lipid metabolism and antioxidants.
      • The availability and safety of SIRT activators provide opportunity to better understand the role of SIRTs in atherosclerosis.

      Abstract

      The sirtuins, silent mating-type information regulation 2 (SIRTs), are a family of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases with important roles in regulating energy metabolism and senescence. Activation of SIRTs appears to have beneficial effects on lipid metabolism and antioxidants, prompting investigation of the roles of these proteins in atherogenesis. Although clinical data are currently limited, the availability and safety of SIRT activators such as metformin and resveratrol provide an excellent opportunity to conduct research to better understand the role of SIRTs in human atherosclerosis. Encouraging observations from preclinical studies necessitate rigorous large, prospective, randomized clinical trials to determine the roles of SIRT activators on the progression of atherosclerosis and ultimately on cardiac outcomes, such as myocardial infarction and mortality.

      Keywords

      Abbreviations:

      ABC (Adenosine triphosphate binding cassette), ABCG (ABC sub-family G member), ADP (Adenosine diphosphate), AMPK (Adenosine monophosphate-activated protein kinase), eNOS (Endothelial nitric oxide synthase), FOXO (Forkhead transcription factor subclass O), HDL-C (High-density lipoprotein cholesterol), HIF1A (Hypoxia-inducible factor 1A), HUVEC (Human umbilical vein endothelial cells), LDL-C (Low-density lipoprotein cholesterol), LDLR (Low-density lipoprotein receptor), LOX-1 (Lectin-like oxidized low-density lipoprotein receptor-1), LXR (Liver X receptor), MnSOD (Manganese-dependent superoxide dismutase), NAD (Nicotinamide adenine dinucleotide), NADPH (Nicotinamide adenine dinucleotide phosphate (reduced form)), N-CoR (Nuclear receptor co-repressor), NF-κB (Nuclear factor κB), NFATc2 (Nuclear factor of activated T cells 2), ox-LDL (Oxidized low-density lipoprotein), p53 (Tumor protein 53), PCSK9 (Proprotein convertase subtilisin/kexin 9), PGC-1α (Peroxisome proliferator-activated receptor-γ co-activator-1α), ROS (Reactive oxygen species), SIRT (Silent mating-type information regulation), SOD2 (Superoxide dismutase 2), SR-B1 (Scavenger receptor class B type I), STAT3 (Signal transducer and activator of transcription-3), VCAM-1 (Vascular cell adhesion molecule-1)
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