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
Oral Abstract PresentationsSession Title: Concurrent Session IV D - Carotid Artery Disease

Abstract 83: Molecular Mechanism of Aortic Aneurysm Formation in Fibulin-4--Deficient Mice

Yoshito Yamashiro, Jianbin Huang, Hamid Mirzaei, Hiromi Yanagisawa
Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;32:A83
Yoshito Yamashiro
Molecular Biology, UT Southwestern Med Cntr, Dallas, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jianbin Huang
Molecular Biology, UT Southwestern Med Cntr, Dallas, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hamid Mirzaei
UT Southwestern Med Cntr, Dallas, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiromi Yanagisawa
Molecular Biology, UT Southwestern Med Cntr, Dallas, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics

Jump to

  • Article
  • Info & Metrics
  • eLetters
Loading

Abstract

Background: Fibulin-4 (Fbln4) is a secreted extracellular matrix protein, which is expressed in blood vessels and associated with microfibrils surrounding elastic fibers. Fbln4-null mice exhibit perinatal lethality with rupture of aortic aneurysm and a marked disruption of elastic fibers, and these phenotypes were recapitulated by smooth muscle cell (SMC)-specific deletion of Fbln4 in vivo (Fbln4SMKO). Severe aneurysms developed exclusively in the ascending aorta at postnatal day 90 (P90) and vascular SMCs were hyper-proliferative and failed to fully differentiate in the Fbln4SMKO aorta.

Objective: To elucidate the molecular mechanism that initiates the aneurysmal change in Fbln4SMKO mice, we performed proteomics analysis of Fbln4-deficient (Fbln4-/-) SMCs and compared with wild-type SMCs.

Methods: The early stage of ascending aneurysm was evaluated in Fbln4SMKO mice using microscopic methods and immunohistochemistry. The protein expression profiles were obtained from postnatal day (P) 7 wild-type and Fbln4-/- SMCs by two-dimensional fluorescence difference gel electrophoresis. Several differentially expressed proteins were identified by mass spectrometry and validated using qPCR and Western blot analysis.

Results: Macroscopic observation revealed that the ascending aorta dilatation was not observed at P7 but became detectable at P14. Histologically, however, focal lesion of SMC proliferation was already noticeable in the sub-endothelial region at P7 and became evident at P14 with a thickened aortic media. Differential proteomic analysis showed that molecules involved in actin dynamics, including gelsolin, ezrin/radixin/moesin (ERM) protein, cofilin-2, and Rho GDI were upregulated in Fbln4-/- SMCs. In addition, phosphorylation of cofilin and ERM was increased in Fbln4-/- SMCs. Interestingly, SMC differentiation markers were normally expressed in Fbln4SMKO aortae until P7.

Conclusion: Our study indicated that the phenotypic change of SMCs occurred after P7 in the Fbln4SMKO aorta and Fbln4 deficiency contributed to aneurysm formation by facilitating the alteration in actin dynamics. This information will shed light on the molecular mechanism of aneurysm initiation in the Fbln4 deficient SMCs.

  • fibulin-4
  • smooth muscle cell
  • proteomics
  • © 2012 by American Heart Association, Inc.
Back to top

Current Issue

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

Jump to

  • Article
  • Info & Metrics

Article Tools

  • Citation Tools
    Abstract 83: Molecular Mechanism of Aortic Aneurysm Formation in Fibulin-4--Deficient Mice
    Yoshito Yamashiro, Jianbin Huang, Hamid Mirzaei and Hiromi Yanagisawa
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;32:A83, originally published October 20, 2015

    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.
    Abstract 83: Molecular Mechanism of Aortic Aneurysm Formation in Fibulin-4--Deficient Mice
    (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
    Abstract 83: Molecular Mechanism of Aortic Aneurysm Formation in Fibulin-4--Deficient Mice
    Yoshito Yamashiro, Jianbin Huang, Hamid Mirzaei and Hiromi Yanagisawa
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;32:A83, originally published October 20, 2015
    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