Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Nagashima, H. et al.

Nagashima, Aoka, Sakomura, Uto, Sakuta, Aomi, Kurosawa, Hagiwara, Kawana, Kasanuki,

Matrix metalloproteinase 2 is suppressed by trapidil, a CD40-CD40 ligand pathway inhibitor, in human abdominal aortic aneurysm wall.

BACKGROUND: The activation of inflammatory cells and the production of matrix metalloproteinases (MMPs) are important in the pathogenesis of abdominal aortic aneurysm (AAA). Previous studies have demonstrated that the antiplatelet agent trapidil has multiple actions, including suppression of MMP expression through the inhibition of the CD40-CD40 ligand ( CD40-CD40L) pathway in cultured cells. A recent clinical study suggested that trapidil might have functions beyond its antiplatelet action.Methods and results In the present study, we performed immunohistochemical analysis and semiquantitative reverse transcription-polymerase chain reaction to evaluate the effect of trapidil on the production of MMPs in cultured aortic tissues from patients with infrarenal AAA (n = 9) and control patients with aortoiliac occlusive disease (n = 7). The tissue concentrations of both MMP-2 and MMP-9 were significantly higher in AAA walls than in control aortic walls. Both trapidil and an anti-CD154 (CD40L) antibody significantly suppressed the protein production and mRNA expression of MMP-2 but did not inhibit those of MMP-9 in organ cultures of AAA wall specimens. MMP-9 was produced by macrophages and a lot of neutrophils in AAA tissues, whereas MMP-2 was derived from macrophages. CD40 was expressed on macrophages but not on neutrophils, and this expression could explain the differential effect of trapidil on the production of MMP-2 and MMP-9. CONCLUSIONS: Trapidil, a CD40-CD40L pathway inhibitor, suppressed mRNA expression and protein production of MMP-2 in AAA tissues, suggesting a potential therapeutic approach for the prevention or treatment of AAA.[1]

References

Matrix metalloproteinase 2 is suppressed by trapidil, a CD40-CD40 ligand pathway inhibitor, in human abdominal aortic aneurysm wall. Nagashima, H., Aoka, Y., Sakomura, Y., Uto, K., Sakuta, A., Aomi, S., Kurosawa, H., Hagiwara, N., Kawana, M., Kasanuki, H. J. Vasc. Surg. (2004) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.