Article

PDF
Access to the PDF text
Advertising


Free Article !

Archives of cardiovascular diseases
Volume 102, n° S1
page 14 (mars 2009)
Doi : 10.1016/S1875-2136(09)72154-0
Themes et posters

A021 Prevention and stabilization of experimental aortic abdominal aneurysms by cyclosporine
 

S. Michineau, J. Dai, A.-M. Guinault, M. Gervais, E. Allaire
CNRS UMR 7054, Créteil, France 

@@#100979@@
Background

Cyclosporine, an effective immunosuppressive, induces long-term abnormal extracellular matrix deposition and decreases MMP-dependent proteolysis through TGF-beta induction. Overexpression of TGF-beta has been shown to promote wall reconstruction and stabilization of experimental abdominal aortic aneurysms (AAA). We thus evaluated the ability of cyclosporine, possibly through TGF-beta to prevent and stop AAA expansion.

Methods and Results

The effect of cyclosporine on AAA remodeling, TGF-beta and matrix metalloprotease (MMP)-9 expression was evaluated on human AAA explants and in two experimental models of AAA: the periaortic CaCl2 and the xenograft models in mice and rats, respectively. Incubation of human AAA explants during 24h with cyclosporine (1 or 2μg/ml) induced an increase in TGF-beta and a decrease in MMP-9 release in conditioned media. A preventive treatment with cyclosporine (50mg/kg/day, i.p., starting 2 days before AAA generation and maintained for 2 weeks) in CaCl2 model in mice was associated with prevention of AAA development (external diameter: 0.72±0.06 vs 1.10±0.05mm in cyclosporine- and vehicle-treated mice, respectively, p=0.008), preservation of medial elastin and smooth muscle cell content and an increase in TGF-beta and a decrease in MMP-9 aortic content. Furthermore, short-term cyclosporine treatment (5mg/kg/day, s.c., for 7 days starting 2 weeks after xenograft) was sufficient to promote long-term (10 weeks after xenograft) healing and stabilization of already-formed AAA in the rat xenograft model (aortic diameter increase: 11.8±6.0 and 45.2±6.1 % in cyclosporine- and vehicle-treated rats, respectively, p=0.017). This curative effect was accompanied by a decreased infiltration of monocyte/macrophages and T lymphocytes, an induction of aortic TGF-beta and tissue metalloprotease inhibitor-1 and a decrease in aortic MMP-9 mRNA levels.

Conclusions

Cyclosporine induced TGF-beta and inhibited MMP-9 release from human AAA explants. Cyclosporine not only prevented the development of AAA but also stop AAA enlargement in experimental AAA models. These protective effects were associated with increased aortic TGF-beta signaling. We further demonstrated that a short induction treatment with cyclosporine is sufficient to promote long-term AAA stabilization in rats and should thus be considered for treatment of human AAA.

The full text of this article is available in PDF format.
The full text of this article is available in PDF format.
Click here to see it.

Top of the page

© 2009  Elsevier Masson SAS. All Rights Reserved.
EM-CONSULTE.COM is registrered at the CNIL, déclaration n° 1286925.
As per the Law relating to information storage and personal integrity, you have the right to oppose (art 26 of that law), access (art 34 of that law) and rectify (art 36 of that law) your personal data. You may thus request that your data, should it be inaccurate, incomplete, unclear, outdated, not be used or stored, be corrected, clarified, updated or deleted.
Personal information regarding our website's visitors, including their identity, is confidential.
The owners of this website hereby guarantee to respect the legal confidentiality conditions, applicable in France, and not to disclose this data to third parties.
Close
Article Outline
You can move this window by clicking on the headline
@@#110903@@