Skip to main content
  • American Heart Association
  • Science Volunteer
  • Warning Signs
  • Advanced Search
  • Donate

  • Home
  • About this Journal
    • Editorial Board
    • Meet the Editors
    • Editorial Manifesto
    • Impact Factor
    • Journal History
    • General Statistics
  • All Issues
  • Subjects
    • All Subjects
    • Arrhythmia and Electrophysiology
    • Basic, Translational, and Clinical Research
    • Critical Care and Resuscitation
    • Epidemiology, Lifestyle, and Prevention
    • Genetics
    • Heart Failure and Cardiac Disease
    • Hypertension
    • Imaging and Diagnostic Testing
    • Intervention, Surgery, Transplantation
    • Quality and Outcomes
    • Stroke
    • Vascular Disease
  • Browse Features
    • Circulation Research Profiles
    • Trainees & Young Investigators
    • Research Around the World
    • News & Views
    • The NHLBI Page
    • Viewpoints
    • Compendia
    • Reviews
    • Recent Review Series
    • Profiles in Cardiovascular Science
    • Leaders in Cardiovascular Science
    • Commentaries on Cutting Edge Science
    • AHA/BCVS Scientific Statements
    • Abstract Supplements
    • Circulation Research Classics
    • In This Issue Archive
    • Anthology of Images
  • Resources
    • Online Submission/Peer Review
    • Why Submit to Circulation Research
    • Instructions for Authors
    • → Article Types
    • → Manuscript Preparation
    • → Submission Tips
    • → Journal Policies
    • Circulation Research Awards
    • Image Gallery
    • Council on Basic Cardiovascular Sciences
    • Customer Service & Ordering Info
    • International Users
  • AHA Journals
    • AHA Journals Home
    • Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB)
    • Circulation
    • → Circ: Arrhythmia and Electrophysiology
    • → Circ: Genomic and Precision Medicine
    • → Circ: Cardiovascular Imaging
    • → Circ: Cardiovascular Interventions
    • → Circ: Cardiovascular Quality & Outcomes
    • → Circ: Heart Failure
    • Circulation Research
    • Hypertension
    • Stroke
    • Journal of the American Heart Association
  • Impact Factor 13.965
  • Facebook
  • Twitter

  • My alerts
  • Sign In
  • Join

  • Advanced search

Header Publisher Menu

  • American Heart Association
  • Science Volunteer
  • Warning Signs
  • Advanced Search
  • Donate

Circulation Research

  • My alerts
  • Sign In
  • Join

  • Impact Factor 13.965
  • Facebook
  • Twitter
  • Home
  • About this Journal
    • Editorial Board
    • Meet the Editors
    • Editorial Manifesto
    • Impact Factor
    • Journal History
    • General Statistics
  • All Issues
  • Subjects
    • All Subjects
    • Arrhythmia and Electrophysiology
    • Basic, Translational, and Clinical Research
    • Critical Care and Resuscitation
    • Epidemiology, Lifestyle, and Prevention
    • Genetics
    • Heart Failure and Cardiac Disease
    • Hypertension
    • Imaging and Diagnostic Testing
    • Intervention, Surgery, Transplantation
    • Quality and Outcomes
    • Stroke
    • Vascular Disease
  • Browse Features
    • Circulation Research Profiles
    • Trainees & Young Investigators
    • Research Around the World
    • News & Views
    • The NHLBI Page
    • Viewpoints
    • Compendia
    • Reviews
    • Recent Review Series
    • Profiles in Cardiovascular Science
    • Leaders in Cardiovascular Science
    • Commentaries on Cutting Edge Science
    • AHA/BCVS Scientific Statements
    • Abstract Supplements
    • Circulation Research Classics
    • In This Issue Archive
    • Anthology of Images
  • Resources
    • Online Submission/Peer Review
    • Why Submit to Circulation Research
    • Instructions for Authors
    • → Article Types
    • → Manuscript Preparation
    • → Submission Tips
    • → Journal Policies
    • Circulation Research Awards
    • Image Gallery
    • Council on Basic Cardiovascular Sciences
    • Customer Service & Ordering Info
    • International Users
  • AHA Journals
    • AHA Journals Home
    • Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB)
    • Circulation
    • → Circ: Arrhythmia and Electrophysiology
    • → Circ: Genomic and Precision Medicine
    • → Circ: Cardiovascular Imaging
    • → Circ: Cardiovascular Interventions
    • → Circ: Cardiovascular Quality & Outcomes
    • → Circ: Heart Failure
    • Circulation Research
    • Hypertension
    • Stroke
    • Journal of the American Heart Association
Cellular Biology

Sirt3 Impairment and SOD2 Hyperacetylation in Vascular Oxidative Stress and HypertensionNovelty and Significance

Anna E. Dikalova, Hana A. Itani, Rafal R. Nazarewicz, William G. McMaster, Charles R. Flynn, Roman Uzhachenko, Joshua P. Fessel, Jorge L. Gamboa, David G. Harrison, Sergey I. Dikalov
Download PDF
https://doi.org/10.1161/CIRCRESAHA.117.310933
Circulation Research. 2017;121:564-574
Originally published July 6, 2017
Anna E. Dikalova
From the Division of Clinical Pharmacology (A.E.D., H.A.I., R.R.N., W.G.M., R.U., J.P.F., J.L.G., D.G.H., S.I.D.) and Department of Surgery (C.R.F.), Vanderbilt University Medical Center, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hana A. Itani
From the Division of Clinical Pharmacology (A.E.D., H.A.I., R.R.N., W.G.M., R.U., J.P.F., J.L.G., D.G.H., S.I.D.) and Department of Surgery (C.R.F.), Vanderbilt University Medical Center, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rafal R. Nazarewicz
From the Division of Clinical Pharmacology (A.E.D., H.A.I., R.R.N., W.G.M., R.U., J.P.F., J.L.G., D.G.H., S.I.D.) and Department of Surgery (C.R.F.), Vanderbilt University Medical Center, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William G. McMaster
From the Division of Clinical Pharmacology (A.E.D., H.A.I., R.R.N., W.G.M., R.U., J.P.F., J.L.G., D.G.H., S.I.D.) and Department of Surgery (C.R.F.), Vanderbilt University Medical Center, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Charles R. Flynn
From the Division of Clinical Pharmacology (A.E.D., H.A.I., R.R.N., W.G.M., R.U., J.P.F., J.L.G., D.G.H., S.I.D.) and Department of Surgery (C.R.F.), Vanderbilt University Medical Center, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roman Uzhachenko
From the Division of Clinical Pharmacology (A.E.D., H.A.I., R.R.N., W.G.M., R.U., J.P.F., J.L.G., D.G.H., S.I.D.) and Department of Surgery (C.R.F.), Vanderbilt University Medical Center, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joshua P. Fessel
From the Division of Clinical Pharmacology (A.E.D., H.A.I., R.R.N., W.G.M., R.U., J.P.F., J.L.G., D.G.H., S.I.D.) and Department of Surgery (C.R.F.), Vanderbilt University Medical Center, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jorge L. Gamboa
From the Division of Clinical Pharmacology (A.E.D., H.A.I., R.R.N., W.G.M., R.U., J.P.F., J.L.G., D.G.H., S.I.D.) and Department of Surgery (C.R.F.), Vanderbilt University Medical Center, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David G. Harrison
From the Division of Clinical Pharmacology (A.E.D., H.A.I., R.R.N., W.G.M., R.U., J.P.F., J.L.G., D.G.H., S.I.D.) and Department of Surgery (C.R.F.), Vanderbilt University Medical Center, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sergey I. Dikalov
From the Division of Clinical Pharmacology (A.E.D., H.A.I., R.R.N., W.G.M., R.U., J.P.F., J.L.G., D.G.H., S.I.D.) and Department of Surgery (C.R.F.), Vanderbilt University Medical Center, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Tables
  • Supplemental Materials
  • Info & Metrics

Jump to

  • Article
    • Abstract
    • Introduction
    • Methods
    • Results
    • Discussion
    • Disclosures
    • Acknowledgments
    • Sources Of Funding
    • Footnotes
    • References
  • Figures & Tables
  • Supplemental Materials
  • Info & Metrics
  • eLetters
Loading

Figures

  • Figure 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 1.

    Effect of Sirt3 depletion on angiotensin II (Ang II)-induced hypertension. A, Blood pressure was measured by telemetry in Sirt3−/− or wild-type (WT) littermates on a C57BL/6J strain infused with low-suppressor dose of Ang II (0.3 mg/kg per day). B, Systolic blood pressure measurements in WT C57Bl/6J, Sirt3−/−, and SOD2+/− mice infused with low dose of Ang II (0.3 mg/kg per day) or saline as vehicle. *P<0.01 vs sham, **P<0.01 vs WT+Ang II (n=6–8).

  • Figure 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 2.

    Measurements of mitochondrial O2· – in aorta (A), endothelial NO (B), SOD2 acetylation (C), and densitometry ratio of Acetyl-SOD2 to total SOD2 (D) in Sirt3−/− and wild-type (WT) mice. After 14 days of saline or low dose of angiotensin II (Ang II; 0.3 mg/kg per day) infusion, mice were euthanized for aorta isolation for O2· – measurements by MitoSOX and high-performance liquid chromatography (HPLC; A), NO analysis by electron spin resonance (ESR; B),5 or Western blot analysis (C). Figure shows representative Western blots. *P<0.05 vs WT, **P<0.01 vs WT+Ang II (n=6).

  • Figure 3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 3.

    Angiotensin II (Ang II)-induced hypertension (A) and aortic mitochondrial O2· – (B) in wild-type (WT) and mCAT mice. After 14 days of saline or Ang II (0.7 mg/kg per day) infusion, mice were euthanized for isolation of aorta for O2· – measurements by MitoSOX and high-performance liquid chromatography (HPLC). *P<0.01 vs sham, **P<0.01 vs Ang II (n=8). ESR indicates electron spin resonance.

  • Figure 4.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 4.

    SOD2 acetylation (A), aortic SOD2 activity (B), and Sirt3 S-glutathionylation in wild-type (WT) and mCAT mice. After 14 days of saline or angiotensin II (Ang II; 0.7 mg/kd per day) infusion, mice were euthanized for isolation of aorta and kidney. SOD2 acetylation and SOD2 activity were measured in the homogenate of aortic vessel by Western blot and electron spin resonance, correspondingly. Sirt3 S-glutathionylation was determined in isolated kidney mitochondria by Sirt3 immunoprecipitation and Western blot with GSH (glutathione, reduced form) antibodies. Figure shows representative blots from 3 experiments. *P<0.01 vs sham, **P<0.01 vs Ang II (n=8).

  • Figure 5.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 5.

    SOD2 acetylation (A), Sirt3 expression, and mitochondrial O2· – (B through D) in human aortic endothelial cells treated with angiotensin II (Ang II; 10 nmol/L), TNFα (1 nmol/L), or Ang II+TNFα for 24 h prior analysis. Mitochondrial O2· – was measured by mitochondria-targeted probe MitoSOX and accumulation of O2· –-specific product 2-OH-Mito-E+ using high-performance liquid chromatography (HPLC; B, insert).5,51 Human aortic endothelial cells (HAEC) were transfected with scramble or Sirt3 siRNA and were stimulated with Ang II+TNFα before Western blot analysis and measurements of mitochondrial O2· –.5 Ang II and TNFα cooperatively induce SOD2 acetylation and stimulate production of mitochondrial O2· –, which is attenuated by scavenging of mitochondrial H2O2. *P<0.01 vs control, **P<0.01 vs Ang II+TNFα.

  • Figure 6.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 6.

    Inhibition of angiotensin II (Ang II)-induced hypertension and vascular dysfunction by mitochondria-targeted antioxidants. A, Systolic blood pressure in mice infused with saline (sham), Ang II (0.7 mg/kg per day) or treated with mitoEbselen after onset of Ang II-induced hypertension, (B) Western blot of SOD2 acetylation, (C) systolic blood pressure, and (D) acetylcholine-dependent relaxation of aortic vessels isolated from mice infused with Ang II and treated with mitoTEMPO (1.4 mg/kg per day) after onset of hypertension. Results represent mean±SEM (n=4–8). *P<0.01 vs Ang II, **P<0.05 vs wild type (WT)+Ang II (n=4–8).

  • Figure 7.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 7.

    Comparison of aortic SOD2 acetylation (A), aortic SOD2 activity (B), and angiotensin II (Ang II)-induced hypertension in wild-type (WT), mCAT, or Sirt3−/− mice (C). After 14 days of saline or Ang II (0.7 mg/kg per day) infusion, mice were euthanized for isolation of aorta for analysis for Western blot and electron spin resonance analysis of SOD2 acetylation and SOD2 activity5 in aortic homogenates. Equal protein loading in acetyl-SOD2 study was confirmed by β-actin Western blot. Results are mean±SEM (n=4–6). *P<0.01 vs WT (sham), **P<0.01 vs WT+Ang II, #P<0.05 vs WT+Ang II.

  • Figure 8.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 8.

    Representative Western blot analysis of SOD2 acetylation, SOD2, and Sirt3 expression in patients with essential hypertension compared with normotensive subjects. *P<0.01 vs normotensive, **P<0.001 vs normotensive (n=6).

Back to top
Previous ArticleNext Article

This Issue

Circulation Research
August 18, 2017, Volume 121, Issue 5
  • Table of Contents
Previous ArticleNext Article

Jump to

  • Article
    • Abstract
    • Introduction
    • Methods
    • Results
    • Discussion
    • Disclosures
    • Acknowledgments
    • Sources Of Funding
    • Footnotes
    • References
  • Figures & Tables
  • Supplemental Materials
  • Info & Metrics

Article Tools

  • Print
  • Citation Tools
    Sirt3 Impairment and SOD2 Hyperacetylation in Vascular Oxidative Stress and HypertensionNovelty and Significance
    Anna E. Dikalova, Hana A. Itani, Rafal R. Nazarewicz, William G. McMaster, Charles R. Flynn, Roman Uzhachenko, Joshua P. Fessel, Jorge L. Gamboa, David G. Harrison and Sergey I. Dikalov
    Circulation Research. 2017;121:564-574, originally published July 6, 2017
    https://doi.org/10.1161/CIRCRESAHA.117.310933

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
  •  Download Powerpoint
  • Article Alerts
    Log in to Email Alerts with your email address.
  • Save to my folders

Share this Article

  • Email

    Thank you for your interest in spreading the word on Circulation Research.

    NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

    Enter multiple addresses on separate lines or separate them with commas.
    Sirt3 Impairment and SOD2 Hyperacetylation in Vascular Oxidative Stress and HypertensionNovelty and Significance
    (Your Name) has sent you a message from Circulation Research
    (Your Name) thought you would like to see the Circulation Research web site.
  • Share on Social Media
    Sirt3 Impairment and SOD2 Hyperacetylation in Vascular Oxidative Stress and HypertensionNovelty and Significance
    Anna E. Dikalova, Hana A. Itani, Rafal R. Nazarewicz, William G. McMaster, Charles R. Flynn, Roman Uzhachenko, Joshua P. Fessel, Jorge L. Gamboa, David G. Harrison and Sergey I. Dikalov
    Circulation Research. 2017;121:564-574, originally published July 6, 2017
    https://doi.org/10.1161/CIRCRESAHA.117.310933
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo

Related Articles

Cited By...

Subjects

  • Cardiology
    • Etiology
      • Hypertension
        • Hypertension
  • Basic, Translational, and Clinical Research
    • Metabolism
    • Oxidant Stress
    • Endothelium/Vascular Type/Nitric Oxide

Circulation Research

  • About Circulation Research
  • Editorial Board
  • Instructions for Authors
  • Abstract Supplements
  • AHA Statements and Guidelines
  • Permissions
  • Reprints
  • Email Alerts
  • Open Access Information
  • AHA Journals RSS
  • AHA Newsroom

Editorial Office Address:
3355 Keswick Rd
Main Bldg 103
Baltimore, MD 21211
CircRes@circresearch.org

Information for:
  • Advertisers
  • Subscribers
  • Subscriber Help
  • Institutions / Librarians
  • Institutional Subscriptions FAQ
  • International Users
American Heart Association Learn and Live
National Center
7272 Greenville Ave.
Dallas, TX 75231

Customer Service

  • 1-800-AHA-USA-1
  • 1-800-242-8721
  • Local Info
  • Contact Us

About Us

Our mission is to build healthier lives, free of cardiovascular diseases and stroke. That single purpose drives all we do. The need for our work is beyond question. Find Out More about the American Heart Association

  • Careers
  • SHOP
  • Latest Heart and Stroke News
  • AHA/ASA Media Newsroom

Our Sites

  • American Heart Association
  • American Stroke Association
  • For Professionals
  • More Sites

Take Action

  • Advocate
  • Donate
  • Planned Giving
  • Volunteer

Online Communities

  • AFib Support
  • Garden Community
  • Patient Support Network
  • Professional Online Network

Follow Us:

  • Follow Circulation on Twitter
  • Visit Circulation on Facebook
  • Follow Circulation on Google Plus
  • Follow Circulation on Instagram
  • Follow Circulation on Pinterest
  • Follow Circulation on YouTube
  • Rss Feeds
  • Privacy Policy
  • Copyright
  • Ethics Policy
  • Conflict of Interest Policy
  • Linking Policy
  • Diversity
  • Careers

©2018 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. The American Heart Association is a qualified 501(c)(3) tax-exempt organization.
*Red Dress™ DHHS, Go Red™ AHA; National Wear Red Day ® is a registered trademark.

  • PUTTING PATIENTS FIRST National Health Council Standards of Excellence Certification Program
  • BBB Accredited Charity
  • Comodo Secured