Abstract 5540: Clarithromycin Attenuates Periodontal Bacteria-Induced Abdominal Aortic Aneurysms With Altered Expression of Matrix Metalloproteinases
Background: Matrix metalloproteinase (MMP) activity is known to be up-regulated in the abdominal aortic aneurysm (AAA). Periodontopathic bacteria were detected at a high rate of specimens of aortic walls from AAA patients. A major macrolide antibiotic, clarithromycin (CAM) has many biological functions including MMP regulation. However, little is known about the effect of CAM in AAA via MMPs. Thus, our purpose was to clarify the role of MMPs regulated by CAM in the progression of periodontopathic bacteria-induced AAA.
Methods and results: AAA was produced by periaortic application of 0.25M CaCl2 and subcutaneous infection of Porphyromonas gingivalis (Pg). We administered CAM (100mg/kg) to mice with AAA once a day for 28 days after CaCl2 application. After the infection with Pg, the plasma level of anti-Pg immunoglobulin-G was increased 2.1-fold (once infected) to 4.0-fold (repeatedly-infected) than the native. Four weeks after application of CaCl2, vehicle-treated mice showed the significant increase in aortic diameter (71±5%). However, CAM treatment significantly suppressed AAA development (12±1%). The CAM-treated mice showed the suppressed plasma level of MMP-9 (71±44 ng/ml) compared to control mice (91±22 ng/ml) using enzyme-linked immunosorbent assay (ELISA). As a compensatory action, the CAM-treated mice also exhibited less plasma level of tissue inhibitor of metalloproteinase (TIMP)-1 (1.96 ng/ml) than control (2.29 ng/ml) by ELISA.
Conclusion: These findings demonstrated that CAM prevented Pg-induced AAA development through the suppression of macrophage derived MMP production. Therefore, CAM could be clinically applicable for prevention of AAA development.