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

  • Home
  • About this Journal
    • Editorial Board
    • Meet the Editors
    • ATVB 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
    • Cover Art Award
    • ATVB Early Career Award
    • ATVB in Focus
    • Recent Brief Reviews of ATVB
    • Lecture Series
    • Collections
    • Recent Highlights of ATVB
    • Commentaries
    • Browse Abstracts
    • Insight into ATVB Authors
  • Resources
    • Instructions for Authors
    • Online Submission/Peer Review Site
    • Council on ATVB
    • Permissions and Rights Q&A
    • AHA Guidelines and Statements
    • Customer Service and Ordering Information
    • Author Reprints
    • International Users
    • AHA Newsroom
  • 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
  • Facebook
  • LinkedIn
  • Twitter

  • My alerts
  • Sign In
  • Join

  • Advanced search

Header Publisher Menu

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

Arteriosclerosis, Thrombosis, and Vascular Biology

  • My alerts
  • Sign In
  • Join

  • Facebook
  • LinkedIn
  • Twitter
  • Home
  • About this Journal
    • Editorial Board
    • Meet the Editors
    • ATVB 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
    • Cover Art Award
    • ATVB Early Career Award
    • ATVB in Focus
    • Recent Brief Reviews of ATVB
    • Lecture Series
    • Collections
    • Recent Highlights of ATVB
    • Commentaries
    • Browse Abstracts
    • Insight into ATVB Authors
  • Resources
    • Instructions for Authors
    • Online Submission/Peer Review Site
    • Council on ATVB
    • Permissions and Rights Q&A
    • AHA Guidelines and Statements
    • Customer Service and Ordering Information
    • Author Reprints
    • International Users
    • AHA Newsroom
  • 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
Original Research

ATG16L1 Expression in Carotid Atherosclerotic Plaques Is Associated With Plaque Vulnerability

Joelle Magné, Peter Gustafsson, Hong Jin, Lars Maegdefessel, Kjell Hultenby, Annika Wernerson, Per Eriksson, Anders Franco-Cereceda, Petri T. Kovanen, Isabel Gonçalves,, Ewa Ehrenborg
Download PDF
https://doi.org/10.1161/ATVBAHA.114.304840
Arteriosclerosis, Thrombosis, and Vascular Biology. 2015;ATVBAHA.114.304840
Originally published March 12, 2015
Joelle Magné
From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital (J.M., P.G., H.J., L.M., P.E., E.E.), Division of Clinical Research Center, Department of Laboratory Medicine (K.H.), Division of Renal Medicine, Department of Clinical Science, Technology and Intervention (A.W.), Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Wihuri Research Institute, Helsinki, Finland (P.T.K.); and Experimental Cardiovascular Research Group and Cardiology Department, Skåne University Hospital, Clinical Research Center, Clinical Sciences Malmö, Lund University, Sweden (I.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter Gustafsson
From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital (J.M., P.G., H.J., L.M., P.E., E.E.), Division of Clinical Research Center, Department of Laboratory Medicine (K.H.), Division of Renal Medicine, Department of Clinical Science, Technology and Intervention (A.W.), Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Wihuri Research Institute, Helsinki, Finland (P.T.K.); and Experimental Cardiovascular Research Group and Cardiology Department, Skåne University Hospital, Clinical Research Center, Clinical Sciences Malmö, Lund University, Sweden (I.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hong Jin
From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital (J.M., P.G., H.J., L.M., P.E., E.E.), Division of Clinical Research Center, Department of Laboratory Medicine (K.H.), Division of Renal Medicine, Department of Clinical Science, Technology and Intervention (A.W.), Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Wihuri Research Institute, Helsinki, Finland (P.T.K.); and Experimental Cardiovascular Research Group and Cardiology Department, Skåne University Hospital, Clinical Research Center, Clinical Sciences Malmö, Lund University, Sweden (I.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lars Maegdefessel
From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital (J.M., P.G., H.J., L.M., P.E., E.E.), Division of Clinical Research Center, Department of Laboratory Medicine (K.H.), Division of Renal Medicine, Department of Clinical Science, Technology and Intervention (A.W.), Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Wihuri Research Institute, Helsinki, Finland (P.T.K.); and Experimental Cardiovascular Research Group and Cardiology Department, Skåne University Hospital, Clinical Research Center, Clinical Sciences Malmö, Lund University, Sweden (I.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kjell Hultenby
From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital (J.M., P.G., H.J., L.M., P.E., E.E.), Division of Clinical Research Center, Department of Laboratory Medicine (K.H.), Division of Renal Medicine, Department of Clinical Science, Technology and Intervention (A.W.), Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Wihuri Research Institute, Helsinki, Finland (P.T.K.); and Experimental Cardiovascular Research Group and Cardiology Department, Skåne University Hospital, Clinical Research Center, Clinical Sciences Malmö, Lund University, Sweden (I.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Annika Wernerson
From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital (J.M., P.G., H.J., L.M., P.E., E.E.), Division of Clinical Research Center, Department of Laboratory Medicine (K.H.), Division of Renal Medicine, Department of Clinical Science, Technology and Intervention (A.W.), Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Wihuri Research Institute, Helsinki, Finland (P.T.K.); and Experimental Cardiovascular Research Group and Cardiology Department, Skåne University Hospital, Clinical Research Center, Clinical Sciences Malmö, Lund University, Sweden (I.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Per Eriksson
From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital (J.M., P.G., H.J., L.M., P.E., E.E.), Division of Clinical Research Center, Department of Laboratory Medicine (K.H.), Division of Renal Medicine, Department of Clinical Science, Technology and Intervention (A.W.), Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Wihuri Research Institute, Helsinki, Finland (P.T.K.); and Experimental Cardiovascular Research Group and Cardiology Department, Skåne University Hospital, Clinical Research Center, Clinical Sciences Malmö, Lund University, Sweden (I.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anders Franco-Cereceda
From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital (J.M., P.G., H.J., L.M., P.E., E.E.), Division of Clinical Research Center, Department of Laboratory Medicine (K.H.), Division of Renal Medicine, Department of Clinical Science, Technology and Intervention (A.W.), Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Wihuri Research Institute, Helsinki, Finland (P.T.K.); and Experimental Cardiovascular Research Group and Cardiology Department, Skåne University Hospital, Clinical Research Center, Clinical Sciences Malmö, Lund University, Sweden (I.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Petri T. Kovanen
From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital (J.M., P.G., H.J., L.M., P.E., E.E.), Division of Clinical Research Center, Department of Laboratory Medicine (K.H.), Division of Renal Medicine, Department of Clinical Science, Technology and Intervention (A.W.), Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Wihuri Research Institute, Helsinki, Finland (P.T.K.); and Experimental Cardiovascular Research Group and Cardiology Department, Skåne University Hospital, Clinical Research Center, Clinical Sciences Malmö, Lund University, Sweden (I.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Isabel Gonçalves,
From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital (J.M., P.G., H.J., L.M., P.E., E.E.), Division of Clinical Research Center, Department of Laboratory Medicine (K.H.), Division of Renal Medicine, Department of Clinical Science, Technology and Intervention (A.W.), Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Wihuri Research Institute, Helsinki, Finland (P.T.K.); and Experimental Cardiovascular Research Group and Cardiology Department, Skåne University Hospital, Clinical Research Center, Clinical Sciences Malmö, Lund University, Sweden (I.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ewa Ehrenborg
From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital (J.M., P.G., H.J., L.M., P.E., E.E.), Division of Clinical Research Center, Department of Laboratory Medicine (K.H.), Division of Renal Medicine, Department of Clinical Science, Technology and Intervention (A.W.), Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Wihuri Research Institute, Helsinki, Finland (P.T.K.); and Experimental Cardiovascular Research Group and Cardiology Department, Skåne University Hospital, Clinical Research Center, Clinical Sciences Malmö, Lund University, Sweden (I.G.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Supplemental Materials
  • Info & Metrics
  • eLetters

Jump to

  • Article
  • Supplemental Materials
  • Info & Metrics
  • eLetters
Loading

Abstract

Objective—Autophagy has emerged as a cell survival mechanism critical for cellular homeostasis, which may play a protective role in atherosclerosis. ATG16L1, a protein essential for early stages of autophagy, has been implicated in the pathogenesis of Crohn’s disease. However, it is unknown whether ATG16L1 is involved in atherosclerosis. Our aim was to analyze ATG16L1 expression in carotid atherosclerotic plaques in relation to markers of plaque vulnerability.

Approach and Results—Histological analysis of 143 endarterectomized human carotid atherosclerotic plaques revealed that ATG16L1 was expressed in areas surrounding the necrotic core and the shoulder regions. Double immunofluorescence labeling revealed that ATG16L1 was abundantly expressed in phagocytic cells (CD68), endothelial cells (CD31), and mast cells (tryptase) in human advanced plaques. ATG16L1 immunogold labeling was predominantly observed in endothelial cells and foamy smooth muscle cells of the plaques. ATG16L1 protein expression correlated with plaque content of proinflammatory cytokines and matrix metalloproteinases. Analysis of Atg16L1 at 2 distinct stages of the atherothrombotic process in a murine model of plaque vulnerability by incomplete ligation and cuff placement in carotid arteries of apolipoprotein-E-deficient mice revealed a strong colocalization of Atg16L1 and smooth muscle cells only in early atherosclerotic lesions. An increase in ATG16L1 expression and autophagy flux was observed during foam cell formation in human macrophages using oxidized-LDL.

Conclusions—Taken together, this study shows that ATG16L1 protein expression is associated with foam cell formation and inflamed plaque phenotype and could contribute to the development of plaque vulnerability at earlier stages of the atherogenic process.

  • ATG16L1
  • atherosclerosis
  • autophagy
  • carotid plaque
  • Received October 30, 2014.
  • Accepted February 27, 2015.
  • © 2015 American Heart Association, Inc.
Back to top
Next Article

Current Issue

Arteriosclerosis, Thrombosis, and Vascular Biology
April 2018, Volume 38, Issue 4
  • Table of Contents
Next Article

Jump to

  • Article
  • Supplemental Materials
  • Info & Metrics
  • eLetters

Article Tools

  • Print
  • Citation Tools
    ATG16L1 Expression in Carotid Atherosclerotic Plaques Is Associated With Plaque Vulnerability
    Joelle Magné, Peter Gustafsson, Hong Jin, Lars Maegdefessel, Kjell Hultenby, Annika Wernerson, Per Eriksson, Anders Franco-Cereceda, Petri T. Kovanen, Isabel Gonçalves, and Ewa Ehrenborg
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2015;ATVBAHA.114.304840, originally published March 12, 2015
    https://doi.org/10.1161/ATVBAHA.114.304840

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
  • 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 Arteriosclerosis, Thrombosis, and Vascular Biology.

    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.
    ATG16L1 Expression in Carotid Atherosclerotic Plaques Is Associated With Plaque Vulnerability
    (Your Name) has sent you a message from Arteriosclerosis, Thrombosis, and Vascular Biology
    (Your Name) thought you would like to see the Arteriosclerosis, Thrombosis, and Vascular Biology web site.
  • Share on Social Media
    ATG16L1 Expression in Carotid Atherosclerotic Plaques Is Associated With Plaque Vulnerability
    Joelle Magné, Peter Gustafsson, Hong Jin, Lars Maegdefessel, Kjell Hultenby, Annika Wernerson, Per Eriksson, Anders Franco-Cereceda, Petri T. Kovanen, Isabel Gonçalves, and Ewa Ehrenborg
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2015;ATVBAHA.114.304840, originally published March 12, 2015
    https://doi.org/10.1161/ATVBAHA.114.304840
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo

Related Articles

Cited By...

Subjects

  • Basic, Translational, and Clinical Research
    • Mechanisms
    • Pathophysiology
    • Cell Biology/Structural Biology

Arteriosclerosis, Thrombosis, and Vascular Biology

  • About ATVB
  • Instructions for Authors
  • AHA CME
  • Meeting Abstracts
  • Permissions
  • Email Alerts
  • Open Access Information
  • AHA Journals RSS
  • AHA Newsroom

Contact the Editorial Office:
email: atvb@atvb.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