Complement factor C5a as mast cell activator mediates vascular remodelling in vein graft disease

de Vries, Margreet R., Wezel, Anouk, Schepers, Abbey, van Santbrink, Peter J., Woodruff, Trent M., Niessen, Hans W. M., Hamming, Jaap F., Kuiper, Johan, Bot, Ilze and Quax, Paul H. A. (2013) Complement factor C5a as mast cell activator mediates vascular remodelling in vein graft disease. Cardiovascular Research, 97 2: 311-320. doi:10.1093/cvr/cvs312


Author de Vries, Margreet R.
Wezel, Anouk
Schepers, Abbey
van Santbrink, Peter J.
Woodruff, Trent M.
Niessen, Hans W. M.
Hamming, Jaap F.
Kuiper, Johan
Bot, Ilze
Quax, Paul H. A.
Title Complement factor C5a as mast cell activator mediates vascular remodelling in vein graft disease
Journal name Cardiovascular Research   Check publisher's open access policy
ISSN 0008-6363
1755-3245
Publication date 2013-02
Year available 2012
Sub-type Article (original research)
DOI 10.1093/cvr/cvs312
Volume 97
Issue 2
Start page 311
End page 320
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2013
Language eng
Formatted abstract
Aims: Failure of vein graft conduits due to vein graft thickening, accelerated atherosclerosis, and subsequent plaque rupture is applicable to 50% of all vein grafts within 10 years. New potential therapeutic targets to treat vein graft disease may be found in components of the innate immune system, such as mast cells and complement factors, which are known to be involved in atherosclerosis and plaque destabilization. Interestingly, mast cells can be activated by complement factor C5a and, therefore, a direct role for C5a-mediated mast cell activation in vein graft disease is anticipated. We hypothesize that C5a-mediated mast cell activation is involved in the development and destabilization of vein graft lesions.

Methods and Results: Mast cells accumulated in time in murine vein graft lesions, and C5a and C5a-receptor (CD88) expression was up-regulated during vein graft disease in apolipoprotein E-deficient mice. Mast cell activation with dinitrophenyl resulted in a profound increase in vein graft thickening and in the number of plaque disruptions. C5a application enhanced vein graft lesion formation, while treatment with a C5a-receptor antagonist resulted in decreased vein graft disease. C5a most likely exerts its function via mast cell activation since the mast cell inhibitor cromolyn totally blocked C5a-enhanced vein graft disease.

Conclusion: These data provide evidence that complement factor C5a-induced mast cell activation is highly involved in vein graft disease, which identifies new targets to prevent vein graft disease.
Keyword Atherosclerosis
Vein graft disease
Venous bypass
Mast cells
Complement factor C5a
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Online publish-ahead-of-print: 14 October 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biomedical Sciences Publications
 
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