Adrenomedullin in mast cells of abdominal aortic aneurysm.
OBJECTIVE
Produced by vascular walls, adrenomedullin (AM) exerts antifibrotic actions in the process of cardiovascular remodeling. The purpose of this study was to examine the pathophysiological role of AM in the development of human abdominal aortic aneurysm (AAA).


RESULTS
Immunohistochemical analyses revealed that vascular smooth muscle cells in the media were positive for AM in the early stage of atherosclerotic aorta. Intense immunoreactivity was observed in mast cells of the outer media and adventitia of AAA, and the number of mast cells was greater (p < 0.01) in AAA than in atherosclerotic aorta without any aneurysmal change. To determine the role of AM in mast cells, we examined cultured human mast cell leukemia line-1 (HMC-1) and fibroblasts isolated from AAA patients. Cultured HMC-1 cells were found to express preproAM gene and release AM peptide into the cultured media. When assessed by collagenase-sensitive [3H]proline incorporation and procollagen type I C-peptide secretion, collagen synthesis in co-culture of HMC-1 and the fibroblasts was reduced by 10(-6) mol/L synthetic AM, while conversely, it increased following blockade of the action of endogenous AM with 10 microg/mL anti-AM monoclonal antibody.


CONCLUSIONS
The present study suggests an anti-fibrotic role for AM released from mast cells, providing new insight into the biological actions of mast cell-derived AM in the development of AAA.
Tsuruda
Toshihiro
T
First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Japan. ttsuruda@med.miyazaki-u.ac.jp
Kato
Johji
J
Hatakeyama
Kinta
K
Yamashita
Atsushi
A
Nakamura
Kunihide
K
Imamura
Takuroh
T
Kitamura
Kazuo
K
Onitsuka
Toshio
T
Asada
Yujiro
Y
Eto
Tanenao
T
D053607:Adrenomedullin; D001012:Aorta, Abdominal / Q000276:immunology*; D017544:Aortic Aneurysm, Abdominal / Q000276:immunology / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008407:Mast Cells / Q000276:immunology*; D010455:Peptides / Q000032:analysis / Q000502:physiology*; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010455:Peptides; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; C112034:preproadrenomedullin; D053607:Adrenomedullin; D003094:Collagen