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由高血囊引起的内皮功能障碍:不对称二甲基氨基基因的作用

Markus C Stühlinger¹, Roberta K Oka, Eric E Graf

¹University Clinic of Innsbruck, Austria.

|August 13, 2003

概括

在人类中,高水平的同类氨酸 (Hcy) 会增加不对称的二甲基氨基氨酸 (ADMA),这是一种NO合成酶抑制剂. 这导致内皮功能障碍,特别是在患有外围动脉疾病的患者中.

科学领域:

心血管科学心血管科学
内皮细胞生物学内皮细胞生物学
代谢研究研究代谢研究

背景情况:

已知高homocysteinemia会损害内皮功能.
之前的研究表明,同类半氨酸 (Hcy) 通过不对称二甲基氨基 (ADMA) 积累抑制培养内皮细胞的氧化 (NO) 生产.

研究的目的:

调查在体外观察到的Hcy诱导的内皮功能障碍的机制是否也在人类中发挥作用.
评估 metionin 负载对不同人群中的 Hcy,ADMA 水平和内皮功能的影响.

主要方法:

对9名外围动脉疾病患者,9名年龄相匹配的对照人群有动脉样硬化风险,以及5名年轻健康对照人群进行了 metionin 负荷测试.
用支臂动脉的流量介导血管扩张来评估内皮功能.
在甲因负载之前和之后测量了Hcy和ADMA的血度.

主要成果:

在所有研究小组中,氨酸负载显著增加了血Hcy和ADMA水平.
周围动脉疾病患者表现出最高的ADMA度和最明显的流量介导血管扩张减轻后的氨酸负载.
在血Hcy和ADMA度之间,以及在ADMA水平和内皮功能障碍之间观察到正相关性.

结论:

人类的实验性高homocysteinemia导致ADMA水平的增加.
这种ADMA积累与内皮功能障碍有关,严重程度与个体先前存在的心血管健康状况相关.
这些发现支持ADMA作为人类高血糖蛋白质血症诱导的内皮功能障碍的关键调解者.

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