Adventitial mast cells contribute to pathogenesis in the progression of abdominal aortic aneurysm.
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.
Tsuruda
Toshihiro
T
Department of Internal Medicine, Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki 5200 Kihara Kiyotake, Miyazaki 889-1692, Japan. ttsuruda@med.miyazaki-u.ac.jp
Kato
Johji
J
Hatakeyama
Kinta
K
Kojima
Kazushi
K
Yano
Mitsuhiro
M
Yano
Yoshikazu
Y
Nakamura
Kunihide
K
Nakamura-Uchiyama
Fukumi
F
Matsushima
Yoshibumi
Y
Imamura
Takuroh
T
Onitsuka
Toshio
T
Asada
Yujiro
Y
Nawa
Yukifumi
Y
Eto
Tanenao
T
Kitamura
Kazuo
K
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D002122:Calcium Chloride; D002452:Cell Count; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D003238:Connective Tissue / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D011922:Rats, Mutant Strains; D013601:T-Lymphocytes / Q000473:pathology; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D001057:Apolipoproteins E; D062367:ortho-Aminobenzoates; D020780:Matrix Metalloproteinase 9; C012293:tranilast; D002122:Calcium Chloride