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Published on: September 28, 2015
Adrenomedullin in mast cells of abdominal aortic aneurysm
Toshihiro Tsuruda1, Johji Kato, Kinta Hatakeyama
1First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Japan. ttsuruda@med.miyazaki-u.ac.jp
Objectives:
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).
Methods And 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.
Conclusion:
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.
Insights
Adrenomedullin (AM) from mast cells may protect against abdominal aortic aneurysm (AAA) development. This study found AM reduced collagen synthesis in AAA models, suggesting an anti-fibrotic role in AAA pathogenesis.
Area of Science:
- Cardiovascular Biology
- Vascular Remodeling
- Atherosclerosis Research
Background:
- Adrenomedullin (AM) is produced by vascular walls and has antifibrotic effects.
- Cardiovascular remodeling involves complex cellular and molecular changes.
- Human abdominal aortic aneurysm (AAA) is a serious vascular condition.
Purpose of the Study:
- To investigate the pathophysiological role of adrenomedullin (AM) in human abdominal aortic aneurysm (AAA) development.
- To explore the source and function of AM in the context of AAA.
Main Methods:
- Immunohistochemical analysis of AM expression in atherosclerotic aortas and AAA tissues.
- Quantification of mast cells in AAA and control samples.
- In vitro studies using cultured human mast cells (HMC-1) and AAA fibroblasts.
- Assessment of collagen synthesis via [3H]proline incorporation and procollagen type I C-peptide secretion.
- Evaluation of synthetic AM and anti-AM monoclonal antibody effects on collagen synthesis.
Main Results:
- Vascular smooth muscle cells showed AM positivity in early atherosclerosis.
- Mast cells in AAA tissues exhibited intense AM immunoreactivity and were significantly increased compared to controls.
- Cultured mast cells expressed AM gene and released AM peptide.
- Synthetic AM reduced collagen synthesis in co-cultured mast cells and fibroblasts.
- Blocking endogenous AM activity increased collagen synthesis.
Conclusions:
- Mast cell-derived AM plays an anti-fibrotic role in abdominal aortic aneurysm (AAA) development.
- This finding provides novel insights into the biological functions of mast cell-derived AM in AAA pathogenesis.
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