Hannemann Juliane, Roskam Thore I, Eilermann Ina, Siques Patricia, Brito Julio, Böger Rainer
Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Institute of Health Studies, Universidad Arturo Prat, Iquique 1100000, Chile.
J Clin Med. 2020 Apr 9;9(4):1072. doi: 10.3390/jcm9041072.
Asymmetric dimethylarginine (ADMA) inhibits nitric oxide (NO) synthesis. It is a risk marker for cardiovascular events and mortality in patients with cardiometabolic diseases and in population-based studies. Plasma or serum analysis of ADMA may be hampered by pre-analytical sample handling. We validated a dried blood spot (DBS) assay for ADMA and L-arginine and show here that this assay has excellent variabilities and reproducibilities. Filter paper is impregnated with the arginase inhibitor nor-NOHA (N-hydroxy-nor-Arginine) to avoid L-arginine degradation. Clinical validation of this DBS assay confirms elevated ADMA concentration in hemodialysis patients as compared to healthy controls, higher ADMA concentrations in men versus women, and elevated L-arginine concentration in subjects supplemented with L-arginine. The DBS assay was used in a cohort study involving 100 primarily healthy subjects in the Andean region to assess the impact of chronic intermittent hypoxia on ADMA and L-arginine; ADMA DBS concentration at sea level was prospectively associated with pulmonary hypertension after six months of exposure to 3500 m. In a cohort of 753 individuals, L-arginine/ADMA ratio significantly decreased with increasing number of traditional cardiovascular risk factors. Analysis of ADMA and L-arginine in DBS is a reliable and reproducible method for quantitation of these markers in field studies.
不对称二甲基精氨酸（ADMA）可抑制一氧化氮（NO）的合成。在患有心脏代谢疾病的患者以及基于人群的研究中，它是心血管事件和死亡率的风险标志物。对ADMA进行血浆或血清分析可能会受到分析前样本处理的影响。我们验证了一种用于检测ADMA和L-精氨酸的干血斑（DBS）检测方法，在此表明该检测方法具有出色的变异性和重现性。滤纸用精氨酸酶抑制剂N-羟基-nor-精氨酸（nor-NOHA）浸渍，以避免L-精氨酸降解。该DBS检测方法的临床验证证实，与健康对照相比，血液透析患者的ADMA浓度升高，男性的ADMA浓度高于女性，补充L-精氨酸的受试者的L-精氨酸浓度升高。DBS检测方法被用于一项队列研究，该研究涉及安第斯地区100名主要为健康的受试者，以评估慢性间歇性缺氧对ADMA和L-精氨酸的影响；在海拔3500米环境中暴露6个月后，海平面时的ADMA DBS浓度与肺动脉高压呈前瞻性关联。在一个由753人组成的队列中，L-精氨酸/ADMA比值随着传统心血管危险因素数量的增加而显著降低。在现场研究中，分析DBS中的ADMA和L-精氨酸是定量这些标志物的可靠且可重复的方法。
