| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Outline of Final Research Achievements |
We found MMP9 was elevated significantly in blood samples from acute aortic dissection (AAD) patients. Using a novel AAD model by infusing angiotensin II to immature mice that had been received a lysyl oxidase inhibitor, we found the incidence of AAD was reduced significantly following the administration of an MMP inhibitor and was almost blocked completely in MMP9(-/-) mice. Neutrophil depletion also significantly decreased the incidence of AAD. Oxidative stress is upregulated in the AAD aorta and an oxidative stress inhibitor reduced the incidence of AAD and the production of MMP9. Coculture experiments using vascular smooth muscle cells and neutrophils revealed the upregulation of MMP9 by neutrophils following AngII stimulation of VSMCs, which was blocked by ROS inhibitor. These data suggest that AAD is initiated by neutrophils that have infiltrated the aortic intima and released MMP9 in response to angiotensin II and the following oxidative stress upregulation.
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