Published online before print May 1, 2008, doi: 10.1161/CIRCRESAHA.108.173682
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Submitted on May 10, 2007
Revised on April 21, 2008
Accepted on April 23, 2008
Adventitial Mast Cells Contribute to Pathogenesis in the Progression of Abdominal Aortic Aneurysm
Toshihiro Tsuruda *;
From the Department of Internal Medicine (T.T., T.I., T.E., K. Kitamura), Circulatory and Body Fluid Regulation, Faculty of Medicine; Frontier Research Center (J.K.), Department of Pathology (K.H., Y.A.), Department of Cardiovascular, Thoracic and General Surgery (K. Kojima, M.Y., Y.Y., K.N., T.O.), and Department of Parasitology (F.N.-U., Y.N.), Faculty of Medicine, University of Miyazaki; and Research Institute (Y.M.), Saitama Cancer Center, Saitama, Japan.
* To whom correspondence should be addressed. E-mail: ttsuruda{at}med.miyazaki-u.ac.jp.
Abdominal aortic aneurysm (AAA) is histologically characterized by medial degeneration and various degrees of chronic adventitial inflammation, although the mechanisms for progression of aneurysm are poorly understood. In the present study, we carried out histological study of AAA tissues of patients, and interventional animal and cell culture experiments to investigate a role of mast cells in the pathogenesis of AAA. The number of mast cells was found to increase in the outer media or adventitia of human AAA, showing a positive correlation between the cell number and the AAA diameter. Aneurysmal dilatation of the aorta was seen in the control (+/+) rats following periaortic application of calcium chloride (CaCl2) treatment but not in the mast cell–deficient mutant Ws/Ws rats. The AAA formation was accompanied by accumulation of mast cells, T lymphocytes and by activated matrix metalloproteinase 9, reduced elastin levels and augmented angiogenesis in the aortic tissue, but these changes were much less in the Ws/Ws rats than in the controls. Similarly, mast cells were accumulated and activated at the adventitia of aneurysmal aorta in the apolipoprotein E–deficient mice. The pharmacological intervention with the tranilast, an inhibitor of mast cell degranulation, attenuated AAA development in these rodent models. In the cell culture experiment, a mast cell directly augmented matrix metalloproteinase 9 activity produced by the monocyte/macrophage. Collectively, these data suggest that adventitial mast cells play a critical role in the progression of AAA.
Key words: adventitia • inflammation • mast cell • matrix metalloproteinase • aneurysm
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