© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Expression of latent TGF-beta binding proteins and association with TGF-beta1 and fibrillin-1 following arterial injury
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Narooie-Nejad, S. H. Paylakhi, S. Shojaee, Z. Fazlali, M. Rezaei Kanavi, N. Nilforushan, S. Yazdani, F. Babrzadeh, F. Suri, M. Ronaghi, et al. Loss of function mutations in the gene encoding latent transforming growth factor beta binding protein 2, LTBP2, cause primary congenital glaucoma Hum. Mol. Genet., October 15, 2009; 18(20): 3969 - 3977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Wildgruber, W Weiss, H Berger, H-H Eckstein, O Wolf, and P Heider Early endothelial and haematological response to cryoplasty compared with balloon angioplasty of the superficial femoral artery a pilot study Br. J. Radiol., June 1, 2007; 80(954): 430 - 436. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhao, Y. Wen, M. L. Polan, J. Qiao, and B. H. Chen Increased expression of latent TGF-{beta} binding protein-1 and fibrillin-1 in human uterine leiomyomata Mol. Hum. Reprod., May 1, 2007; 13(5): 343 - 349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Ikonomidis, J. A. Jones, J. R. Barbour, R. E. Stroud, L. L. Clark, B. S. Kaplan, A. Zeeshan, J. E. Bavaria, J. H. Gorman III, F. G. Spinale, et al. Expression of Matrix Metalloproteinases and Endogenous Inhibitors Within Ascending Aortic Aneurysms of Patients With Marfan Syndrome Circulation, July 4, 2006; 114(1_suppl): I-365 - I-370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wang, D. Zhao, G. Spinetti, J. Zhang, L.-Q. Jiang, G. Pintus, R. Monticone, and E. G. Lakatta Matrix Metalloproteinase 2 Activation of Transforming Growth Factor-{beta}1 (TGF-{beta}1) and TGF-{beta}1-Type II Receptor Signaling Within the Aged Arterial Wall Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1503 - 1509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wen, M. L. Polan, and B. Chen Do extracellular matrix protein expressions change with cyclic reproductive hormones in pelvic connective tissue from women with stress urinary incontinence? Hum. Reprod., May 1, 2006; 21(5): 1266 - 1273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. C. Carvalho, L. Jonker, M.-J. Goumans, J. Larsson, P. Bouwman, S. Karlsson, P. t. Dijke, H. M. Arthur, and C. L. Mummery Defective paracrine signalling by TGF{beta} in yolk sac vasculature of endoglin mutant mice: a paradigm for hereditary haemorrhagic telangiectasia Development, December 15, 2004; 131(24): 6237 - 6247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dupuis, F. Soubrier, I. Brocheriou, S. Raoux, M. Haloui, L. Louedec, J.-B. Michel, and S. Nadaud Profiling of Aortic Smooth Muscle Cell Gene Expression in Response to Chronic Inhibition of Nitric Oxide Synthase in Rats Circulation, August 17, 2004; 110(7): 867 - 873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Kielty, M. J. Sherratt, and C. A. Shuttleworth Elastic fibres J. Cell Sci., July 15, 2002; 115(14): 2817 - 2828. [Abstract] [Full Text] [PDF]
|
|