Department of Clinical Chemistry, Metabolic Unit, Institute for Cardiovascular Research (ICAR-VU), VU University Medical Center, Amsterdam, The Netherlands.
Atherosclerosis. 2012 Jun;222(2):509-11. doi: 10.1016/j.atherosclerosis.2012.03.009. Epub 2012 Mar 24.
In hyperhomocysteinemia (HHcy), an independent risk factor for cardiovascular diseases, endothelial dysfunction due to reduced bioavailability of nitric oxide is a consistent finding. However, the underlying mechanisms remain unknown. Increased levels of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) have been associated with HHcy, and may contribute, at least in part, for the homocysteine-induced endothelial dysfunction, but whether cystathionine β-synthase (CBS) deficiency is associated with increased ADMA has hardly been investigated. To address this question, we measured total homocysteine (tHcy), ADMA and symmetric dimethylarginine (SDMA) in plasma of 22 adult CBS deficient patients, using established HPLC techniques. Results showed that in CBS deficient patients with elevated levels of tHcy (median (total range): 33 (14-237) μmol/L), both ADMA and SDMA levels were normal. Moreover, tHcy and ADMA concentrations were not correlated (r(s)=0.017, p=0.94). Our results favor the hypothesis that the negative vascular effects of HHcy have an ADMA-independent etiology.
在高同型半胱氨酸血症（HHcy）中，由于一氧化氮生物利用度降低导致内皮功能障碍是一个一致的发现，这是心血管疾病的一个独立危险因素。然而，其潜在机制尚不清楚。一氧化氮合酶抑制剂不对称二甲基精氨酸（ADMA）水平升高与 HHcy 有关，至少部分原因是同型半胱氨酸引起的内皮功能障碍，但胱硫醚β合酶（CBS）缺乏是否与 ADMA 升高有关，几乎没有被研究过。为了解决这个问题，我们使用已建立的 HPLC 技术测量了 22 名成年 CBS 缺乏症患者血浆中的总同型半胱氨酸（tHcy）、ADMA 和对称二甲基精氨酸（SDMA）。结果表明，在 tHcy 水平升高的 CBS 缺乏症患者中（中位数（总范围）：33（14-237）μmol/L），ADMA 和 SDMA 水平均正常。此外，tHcy 和 ADMA 浓度之间没有相关性（r(s)=0.017，p=0.94）。我们的结果支持这样一种假设，即 HHcy 的血管负性作用具有 ADMA 无关的病因。
