Skip Navigation

Cardiovascular Research 2002 53(4):971-983; doi:10.1016/S0008-6363(01)00512-0
© 2002 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Sinha, S.
Right arrow Articles by Kielty, C. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sinha, S.
Right arrow Articles by Kielty, C. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2002, European Society of Cardiology

Expression of latent TGF-beta binding proteins and association with TGF-beta1 and fibrillin-1 following arterial injury

Sanjay Sinhaa,b,1, Anthony M. Heagertyb, C.Adrian Shuttlewortha and Cay M. Kieltya,b,*

aWellcome Trust Centre for Cell-Matrix Research, 2.205 Stopford Building, University of Manchester, Manchester M13 9PT, UK
bDepartment of Medicine, University of Manchester, Oxford Road, Manchester M13 9PT, UK

* Tel.: +44-161-275-5739; fax: +44-161-275-5082 cay.kielty{at}man.ac.uk

Objectives: Transforming growth factor-β (TGF-β), a potent regulator of wound healing and scar formation, is thought to have a key role in the response to arterial injury. Latent TGF-β binding proteins (LTBPs), members of the fibrillin superfamily, govern TGF-β1 release, targeting and activation in vitro and also play a role as structural components of fibrillin-rich microfibrils. Despite the potential of LTBPs to modulate the response to arterial injury through either or both of these mechanisms, as yet their expression and function in the injured vasculature remain poorly defined. Methods: In this study, a porcine model of coronary angioplasty was used to investigate LTBP-1 and LTBP-2 synthesis and their association with TGF-β1 and fibrillin-1. Results: After angioplasty, increased LTBP-1 and LTBP-2 immunostaining was detected in a similar distribution to increased TGF-β1 expression in the neointima and in the neoadventitia. Overnight organ cultures revealed the formation of large latent TGF-β1 complexes containing LTBP-1. Increased LTBP-1 proteolysis after arterial injury correlated with increased active and latent TGF-β levels. LTBP-2 synthesis increased in response to arterial injury but was neither present in large latent complexes nor proteolytically processed. LTBP-1 and LTBP-2 both co-localised to fibrillin-rich fibrillar structures in the neointima and adventitia. Conclusions: These data suggest that LTBP-1 may have a TGF-β1 binding role in the arterial response to injury, and that LTBP-1 and LTBP-2 may have a structural role in association with microfibrils within the developing neointimal lesion. LTBP-1 proteolysis is potentially an important regulatory step for TGF-β activation in the vasculature and inhibition of proteolysis could represent a novel therapeutic modality for controlling the arterial injury response.

KEYWORDS Growth factors; Extracellular matrix; Angioplasty; Coronary circulation; Smooth muscle

1 Current address: University of Virginia, Molecular Physiology and Biological Physics, PO Box 800736, Charlottesville, VA 22908-0736, USA.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.