Adrenomedullin in mast cells of abdominal aortic aneurysm.
Adrenomedullin in mast cells of abdominal aortic aneurysm.
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DOI：
10.1016/j.cardiores.2006.02.003
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发表时间：
2006-04
影响因子：
10.8
通讯作者：
T. Tsuruda;J. Kato;K. Hatakeyama;A. Yamashita;Kunihide Nakamura;T. Imamura;K. Kitamura;T. Onitsuka;Y. Asada;T. Eto
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文献类型：
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作者：
T. Tsuruda;J. Kato;K. Hatakeyama;A. Yamashita;Kunihide Nakamura;T. Imamura;K. Kitamura;T. Onitsuka;Y. Asada;T. Eto
目的肾上腺髓质素(adrenomedullin，AM)由血管壁产生，在心血管重塑过程中发挥抗纤维化作用。本研究旨在探讨AM在人腹主动脉瘤(AAA)发生发展中的病理生理作用。方法和结果免疫组织化学分析显示，动脉粥样硬化早期中膜血管平滑肌细胞AM呈阳性反应。AAA外中膜和外膜肥大细胞呈强阳性反应，且AAA组肥大细胞数量明显多于无动脉瘤样改变的动脉粥样硬化组(P<0.01)。为了确定AM在肥大细胞中的作用，我们检测了培养的人肥大细胞白血病细胞系-1(HMC-1)和从AAA患者分离的成纤维细胞。培养的HMC-1细胞表达前ProAM基因，并向培养上清液中释放AM多肽。胶原酶敏感的[3 H]-Pro掺入和I型胶原C肽分泌检测显示，10−-6mol/L合成AM可使HMC-1与成纤维细胞共培养的胶原合成减少，而用10μg/mLAM单抗阻断内源性AM的作用后，胶原合成增加。结论本研究提示肥大细胞释放的AM具有抗纤维化作用，为进一步研究肥大细胞来源的AM在再生障碍性贫血中的生物学作用提供了新的思路。
ObjectivesProduced 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 resultsImmunohistochemical 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− 6mol/L synthetic AM, while conversely, it increased following blockade of the action of endogenous AM with 10μg/mL anti-AM monoclonal antibody.ConclusionThe 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.