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
In This Issue

In This Issue

Download PDF
https://doi.org/10.1161/RES.0b013e3181fd8052
Circulation Research. 2010;107:939
Originally published October 14, 2010
  • Article
  • Figures & Tables
  • Info & Metrics

Jump to

  • Article
    • Mitochondria and Na+ Channels (p 967)
    • Enhanced Fibroblast–Myocyte Interactions (p 1011)
    • DNA Damage in Atherosclerosis (p 1021)
  • Figures & Tables
  • Info & Metrics
  • eLetters
Loading

Mitochondria and Na+ Channels (p 967)

Liu et al suggest a new way to prevent irregular heartbeats: by keeping a lid on mitochondrial ROS production.

Figure1
  • Download figure
  • Open in new tab
  • Download powerpoint

Maintaining a regular heartbeat depends on the correct functioning of the heart cells' sodium channels. Indeed, syndromes that display aberrant channel function, such as sudden infant death syndrome (SIDS) and Brugada syndrome, are associated with fatal heart arrhythmias. Both SIDS and Brugada syndrome are linked to gene mutations that result in an increase in the levels of NADH. Excessive NADH increases the intracellular production of reactive oxygen species (ROS), which it is believed might structurally damage the sodium channels. Liu et al were interested in discovering the origin of the ROS. Using a variety of chemical inhibitors, they ruled out certain cellular enzymes and molecules as the source and fingered the blame on mitochondria. When mitochondrial ROS production was inhibited, even in the presence of high cytosolic NADH, normal sodium channel conduction was restored. Therapies for SIDS, Brugada, and other arrhythmias have traditionally targeted the dysfunctional sodium channels themselves. The report by Liu et al suggests that an alternative or adjunctive approach might be to block ROS generation by the mitochondria.

Enhanced Fibroblast–Myocyte Interactions (p 1011)

Fibroblasts activated by heart injury do more than just form scars. They also directly interfere with heart cells' electrical activity, say Vasquez et al.

Figure2
  • Download figure
  • Open in new tab
  • Download powerpoint

After a heart injury, cardiac fibroblasts are activated and proliferate quickly to mend the damage. The resulting fibrotic scar was thought to affect the electrophysiology properties of the heart indirectly—by forming a boundary between electrically active muscle cells. But Vasquez and colleagues found that the activated fibroblasts are not so passive after all. A critical step in fibroblast activation is their conversion into myofibroblasts. Myofibroblasts differ from the normal cardiac fibroblasts in their proliferative, migratory, adhesive, and collagen-synthesizing capacities. It now appears they differ in their electrical properties, too. The team showed that compared with regular fibroblasts, myofibroblasts formed more connections with cardiomyocytes and altered the myocytes' conduction velocities and action potential durations. Interestingly, myofibroblast-conditioned culture medium could also affect myocyte electrical activity, indicating that myofibroblasts exert their affect both through cell-to-cell contacts and via secreted factors. Severe arrhythmias can ultimately result in sudden death. Because conversion of fibroblasts to myofibroblasts could potentially distort regular heart rhythm, targeting this conversion could be an effective antiarrhythmic strategy.

DNA Damage in Atherosclerosis (p 1021)

Damaged DNA drives development of atherosclerosis, report Mercer et al.

Figure3
  • Download figure
  • Open in new tab
  • Download powerpoint

DNA damage has been detected in the plaques and circulating cells of patients with atherosclerosis, but whether this damage was a byproduct or the antecedent cause of the disease was unknown. Mercer and colleagues now report data that support the latter possibility. The team showed that mice that were deficient for a DNA repair factor called ATM were prone to accelerated atherosclerosis and to other symptoms of metabolic syndrome, such as hypertension, increased body fat, and glucose intolerance. In the ATM-deficient mice, macrophages and vascular smooth muscle cells (VSMCs)—both of which contribute to plaque formation—displayed increased genomic and mitochondrial DNA damage, as well as increased reactive oxygen species (ROS) production. Transfer of bone marrow cells expressing wild-type levels of ATM improved the accelerated atherosclerosis phenotype. It did not improve the other symptoms, however, most likely because ATM-deficiency caused mitochondrial DNA damage and dysfunction in other tissues, such as liver and pancreas. Mitochondrial dysfunction might be particularly detrimental in metabolic syndrome progression because failing mitochondria produce excessive ROS, which can further damage DNA and worsen dysfunction. Drugs that reduce DNA damage or boost mitochondrial function, or both, could thus be especially effective in preventing atherosclerotic lesion formation and metabolic syndrome.

Written by Ruth Williams

  • © 2010 American Heart Association, Inc.
View Abstract
Back to top
Previous ArticleNext Article

This Issue

Circulation Research
October 15, 2010, Volume 107, Issue 8
  • Table of Contents
Previous ArticleNext Article

Jump to

  • Article
    • Mitochondria and Na+ Channels (p 967)
    • Enhanced Fibroblast–Myocyte Interactions (p 1011)
    • DNA Damage in Atherosclerosis (p 1021)
  • Figures & Tables
  • Info & Metrics

Article Tools

  • Print
  • Citation Tools
    In This Issue
    Circulation Research. 2010;107:939, originally published October 14, 2010
    https://doi.org/10.1161/RES.0b013e3181fd8052

    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.
    In This Issue
    (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
    In This Issue
    Circulation Research. 2010;107:939, originally published October 14, 2010
    https://doi.org/10.1161/RES.0b013e3181fd8052
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo

Related Articles

Cited By...

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