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
Letters to the Editor

Neointimal Cracks (Plaque Rupture?) and Thrombosis in Wrapped Arteries Without Flow

Masafumi Kuzuya, Takeshi Sasaki
Download PDF
https://doi.org/10.1161/01.ATV.0000249619.75202.1e
Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:252
Originally published December 21, 2006
Masafumi Kuzuya
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takeshi Sasaki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters

Jump to

  • Article
    • Acknowledgments
    • References
  • Info & Metrics
  • eLetters
Loading

In Response:

The criticism of Falk et al is based on the lack of evidence of consecutive events in the Sasaki model1: plaque breakdown first, then thrombosis formation. As cited by Falk et al, we have previously demonstrated that the simultaneous treatment of ligation and cuff placement in the mouse carotid artery induced occlusive thrombosis which was accompanied with endothelial cell damage in wild-type mice.2 Falk et al may speculate that thrombus formation in our new rupture model was also mediated through the combined application-induced endothelial damage but not through plaque breakdown, or that plaque disruption and thrombus formation may occur independently. We cannot neglect the possibility that plaque disruption (rupture) may not always be necessary for occlusive thrombus formation in the Sasaki model, although we clearly demonstrated the association of neointima cracks with the thrombus formation. To demonstrate the direct relationship between plaque breakdown and thrombus formation, a careful time course study is needed. However, it is very difficult to clarify the time course of plaque disruption and thrombosis formation, because these two events seem to generate at almost the same time. Fibrous cap, which was stained with smooth muscle cell-marker, was detected in the most of the neointima lesions, and cracks were observed at the fibrous cap region, although there was no necrotic core in the lesions of Sasaki model.1 Nevertheless, we believe that our model is still useful for investigating the pathophysiological mechanisms underlying the development of the vulnerable lesion and plaque rupture of humans, because this model represents similar features observed during the process of human plaque rupture: a reduction of collagen content, the presence of matrix metalloproteinases, an increase in apoptotic cells and inflammatory cells in the plaque lesions before the thrombosis formation, followed by neointima cracks and thrombotic occlusion of the artery at the site of the presumed rupture. These events observed in the Sasaki model appear to be analogous to the events in some parts of human plaque rupture. Obviously, this model does not completely reproduce human plaque rupture, the final event in a long and complex pathophysiological process. However, we should take advantage of beneficial parts in this incomplete model, and should also avoid rejecting animal models simply because they do not generate human-like lesions, as described in the editorial by Jackson.3

Finally, we believe that the plaque vulnerability and rupture in the Sasaki model partially overlap with human disease, and improve several disadvantages in previous models of plaque rupture. This model can be used as a useful model of some aspects of human plaque rupture until an animal model with ideal features of human plaque rupture without the need for artificial manipulations is developed.4

Acknowledgments

Disclosures

None.

References

  1. ↵
    Sasaki T, Kuzuya M, Nakamura K, Cheng XW, Shibata T, Sato K, Iguchi A. A simple method of plaque rupture induction in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2006; 26: 1304–1309.
    OpenUrlAbstract/FREE Full Text
  2. ↵
    Sasaki T, Kuzuya M, Cheng XW, Nakamura K, Tamaya-Mori N, Maeda K, Kanda S, Koike T, Sato K, Iguchi A. A novel model of occlusive thrombus formation in mice. Lab Invest. 2004; 84: 1526–1532.
    OpenUrlCrossRefPubMed
  3. ↵
    Jackson CL. Ruptures of delight? A new mouse model of plaque rupture. Arterioscler Thromb Vasc Biol. 2006; 26: 1191–1192.
    OpenUrlFREE Full Text
  4. ↵
    Cullen P, Baetta R, Bellosta S, Bernini F, Chinetti G, Cignarella A, von Eckardstein A, Exley A, Goddard M, Hofker M, Hurt-Camejo E, Kanters E, Kovanen P, Lorkowski S, McPheat W, Pentikainen M, Rauterberg J, Ritchie A, Staels B, Weitkamp B, de Winther M; MAFAPS Consortium. Rupture of the atherosclerotic plaque: does a good animal model exist? Arterioscler Thromb Vasc Biol. 2003; 23: 535–542.
    OpenUrlAbstract/FREE Full Text
View Abstract
Back to top
Previous ArticleNext Article

This Issue

Arteriosclerosis, Thrombosis, and Vascular Biology
January 2007, Volume 27, Issue 1
  • Table of Contents
Previous ArticleNext Article

Jump to

  • Article
    • Acknowledgments
    • References
  • Info & Metrics
  • eLetters

Article Tools

  • Print
  • Citation Tools
    Neointimal Cracks (Plaque Rupture?) and Thrombosis in Wrapped Arteries Without Flow
    Masafumi Kuzuya and Takeshi Sasaki
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:252, originally published December 21, 2006
    https://doi.org/10.1161/01.ATV.0000249619.75202.1e

    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.
    Neointimal Cracks (Plaque Rupture?) and Thrombosis in Wrapped Arteries Without Flow
    (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
    Neointimal Cracks (Plaque Rupture?) and Thrombosis in Wrapped Arteries Without Flow
    Masafumi Kuzuya and Takeshi Sasaki
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:252, originally published December 21, 2006
    https://doi.org/10.1161/01.ATV.0000249619.75202.1e
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo

Related Articles

Cited By...

Arteriosclerosis, Thrombosis, and Vascular Biology

  • About ATVB
  • 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