Related Experiment Video
Updated: Aug 29, 2026
Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice
Published on: September 28, 2015
Matrix metalloproteinase 2 is suppressed by trapidil, a CD40-CD40 ligand pathway inhibitor, in human abdominal aortic
Hirotaka Nagashima1, Yoshikazu Aoka, Yasunari Sakomura
1Department of Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan. mnagasih@hij.twmu.ac.jp
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.
Insights
Trapidil, an inhibitor of the CD40-CD40 ligand pathway, reduced matrix metalloproteinase-2 (MMP-2) in abdominal aortic aneurysm (AAA) tissues. This suggests trapidil may be a potential therapy for preventing or treating AAA.
Area of Science:
- Vascular Biology
- Inflammation Research
- Drug Discovery
Background:
- Abdominal aortic aneurysm (AAA) pathogenesis involves inflammatory cell activation and matrix metalloproteinase (MMP) production.
- The antiplatelet agent trapidil inhibits MMP expression via the CD40-CD40 ligand (CD40-CD40L) pathway.
- Clinical studies suggest trapidil possesses functions beyond its antiplatelet activity.
Purpose of the Study:
- To investigate the effect of trapidil on MMP production in human AAA tissues.
- To evaluate trapidil's potential as a therapeutic agent for AAA.
Main Methods:
- Immunohistochemical analysis and semiquantitative reverse transcription-polymerase chain reaction were used.
- Organ cultures of aortic tissues from AAA patients and controls were treated with trapidil or an anti-CD40L antibody.
- MMP-2 and MMP-9 protein production and mRNA expression were assessed.
Main Results:
- MMP-2 and MMP-9 concentrations were significantly higher in AAA walls compared to controls.
- Trapidil and anti-CD40L antibody suppressed MMP-2 protein production and mRNA expression.
- Neither agent inhibited MMP-9 production; MMP-2 was macrophage-derived, while MMP-9 was from macrophages and neutrophils.
Conclusions:
- Trapidil inhibits MMP-2 production in AAA tissues by targeting the CD40-CD40L pathway.
- These findings suggest trapidil as a potential therapeutic strategy for AAA prevention or treatment.
