SIRT1 Promotes Endothelium-Dependent Vascular Relaxation by Activating Endothelial Nitric Oxide Synthase
Open accessAbstract
Reduced caloric intake decreases arterial blood pressure in healthy individuals and improves endothelium-dependent vasodilation in obese and overweight individuals. The SIRT1 protein deacetylase mediates many of the effects of calorie restriction (CR) on organismal lifespan and metabolic pathways. However, the role of SIRT1 in regulating endothelium-dependent vasomotor tone is not known. Here we show that SIRT1 promotes endothelium-dependent vasodilation by targeting endothelial nitric oxide synthase (eNOS) for deacetylation. SIRT1 and eNOS colocalize and coprecipitate in endothelial cells, and SIRT1 deacetylates eNOS, stimulating eNOS activity and increasing endothelial nitric oxide (NO). SIRT1-induced increase in endothelial NO is mediated through lysines 496 and 506 in the calmodulin-binding domain of eNOS. Inhibition of SIRT1 in the endothelium of arteries inhibits endothelium-dependent vasodilation and decreases bioavailable NO. Finally, CR of mice leads to deacetylation of eNOS. Our results demonstrate that SIRT1 plays a fundamental role in regulating endothelial NO and endothelium-dependent vascular tone by deacetylating eNOS. Furthermore, our results provide a possible molecular mechanism connecting the effects of CR on the endothelium and vascular tone to SIRT1-mediated deacetylation of eNOS.
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SIRT1 activates eNOS by deacetylation in human vascular cells.
“SIRT1 has been suggested to play an important role since this enzyme activates eNOS by deacetylation in human vascular cells”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Mattagajasingh et al., 2007
Sirtuin-1 plays a positive role in regulating endothelium-dependent vasodilation via deacetylation of lysines 496 and 506 on endothelial nitric oxide synthase.
“Sirtuin-1 plays a positive role in regulating endothelium-dependent vasodilation via the deacetylation of lysines 496 and 506 on endothelial nitric oxide synthase (eNOS) (180).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [180]
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- Authors
- Mattagajasingh, I., Kim, C.-S., Naqvi, A., Yamamori, T., Hoffman, T. A., Jung, S.-B., DeRicco, J., Kasuno, K., & Irani, K.
- Affiliations
- University of Pittsburgh Medical Center (US)
- University of California, Los Angeles (US)
- Corresponding author
- Irani, Kaikobad
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-09-11
- Volume
- 104
- Issue
- 37
- Pages
- 14855-14860
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1976244
- OpenAlex
- W1995188356
- Cited by
- 881
- References
- 23
- Citations by year
- 2026: 34 · 2025: 41 · 2024: 28 · 2023: 36 · 2022: 52 · 2021: 54 · 2020: 47 · 2019: 36 · 2018: 56 · 2017: 46 · 2016: 40 · 2015: 67 · 2014: 59 · 2013: 65 · 2012: 64
- FWCI
- 15.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- SIRT1, endothelial nitric oxide synthase, endothelium-dependent vasodilation, nitric oxide, caloric restriction, calmodulin-binding domain, vascular tone, endothelial cells, protein deacetylase
- MeSH terms
- Animals, Aorta, Thoracic, Cells, Cultured, Chlorocebus aethiops, Endothelium, Vascular, Enzyme Activation, Humans, Nitrates, Nitrites, Recombinant Proteins, Transfection, Umbilical Veins, Vasodilation, DNA, Complementary, COS Cells, RNA Interference, Sirtuins, Rats, Nitric Oxide Synthase Type III, Sirtuin 1
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