Nakayama M, Takahashi K, Murakami O, Shirato K, Shibahara S
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
Peptides. 1999;20(6):769-72. doi: 10.1016/s0196-9781(99)00061-3.
To explore the role of adrenomedullin (ADM) in pathophysiology of ischemic heart disease, we investigated the effects of hypoxia on the production and secretion of ADM in cultured human coronary artery endothelial cells. Treatment with hypoxia (5% CO2/94% N2/1% O2) for 6 and 12 h increased expression levels of ADM mRNA 2.2-fold and fivefold compared with the normoxia control, respectively. The levels of immunoreactive ADM in the media were increased by 12-h hypoxia about fivefold compared with the control (39.0+/-1.1 fmol/10(5) cells per 12 h under hypoxia and 7.9+/-0.4 fmol/10(5) cells per 12 h under normoxia; P<0.01, n = 4, mean +/- SEM). Reverse-phase high-performance liquid chromatography of the extracts of culture media under normoxia and hypoxia showed one major peak eluting in the position of human ADM standard. The production and secretion of ADM were increased in cultured human coronary artery endothelial cells under hypoxia. ADM may therefore play an important pathophysiological role in ischemic heart disease.
为探讨肾上腺髓质素（ADM）在缺血性心脏病病理生理学中的作用，我们研究了缺氧对培养的人冠状动脉内皮细胞中ADM产生和分泌的影响。与常氧对照组相比，缺氧（5%二氧化碳/94%氮气/1%氧气）处理6小时和12小时后，ADM mRNA的表达水平分别增加了2.2倍和5倍。与对照组相比，12小时缺氧使培养基中免疫反应性ADM水平增加了约5倍（缺氧条件下每12小时为39.0±1.1 fmol/10⁵细胞，常氧条件下每12小时为7.9±0.4 fmol/10⁵细胞；P<0.01，n = 4，平均值±标准误）。对常氧和缺氧条件下培养基提取物进行反相高效液相色谱分析，结果显示一个主要峰在人ADM标准品的位置洗脱。缺氧条件下培养的人冠状动脉内皮细胞中ADM的产生和分泌增加。因此，ADM可能在缺血性心脏病中发挥重要的病理生理作用。
