Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
DZHK (German Centre of Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany.
Biomolecules. 2019 Jul 13;9(7):277. doi: 10.3390/biom9070277.
Despite genetic heterogeneity, early manifestation of diastolic dysfunction (DD) is common in hypertrophic cardiomyopathy (HCM). Nitric oxide (NO) may contribute to myocardial relaxation. NO synthases (NOS) use l-arginine (Arg) as a substrate, as asymmetric dimethylarginine (ADMA) is a direct endogenous inhibitor of NOS. This study aimed to analyze the association of Arg and its derivates, i.e., l-homoarginine (hArg), ADMA and symmetric dimethylarginine (SDMA), with DD in HCM patients. In 215 HCM patients (mean age 54 ± 15 years, 58% male) transmitral and mitral annulus velocities were echocardiographically analyzed. Plasma concentrations of Arg derivatives were measured by liquid chromatography tandem-mass spectrometry. In 143 (70%) patients suffering from DD, ADMA showed the strongest association with DD (0.66 ± 0.16, 0.72 ± 0.24, and 0.76 ± 0.26 µmol/L, < 0.01 for trend). In linear regression analyses, positive association per standard deviation increase of ADMA was found with E-wave (beta coefficient (95% confidence interval): 4.72 (0.43-9.01); < 0.05) and mean E/E' (1.76 (0.73-2.79) < 0.001). Associations were adjusted for age, sex, body mass index (BMI), diabetes mellitus, coronary artery disease, and arterial hypertension. Elevated ADMA is associated with the severity of DD in HCM. Higher ADMA level might lead to decreased NO production and thus an impaired myocardial relaxation pattern.
尽管存在遗传异质性，但肥厚型心肌病（HCM）患者常早期出现舒张功能障碍（DD）。一氧化氮（NO）可能有助于心肌舒张。NO 合酶（NOS）以 l-精氨酸（Arg）为底物，而不对称二甲基精氨酸（ADMA）是 NOS 的直接内源性抑制剂。本研究旨在分析 Arg 及其衍生物，即 l-同型精氨酸（hArg）、ADMA 和对称二甲基精氨酸（SDMA）与 HCM 患者 DD 的相关性。在 215 名 HCM 患者（平均年龄 54±15 岁，58%为男性）中，通过超声心动图分析了二尖瓣和二尖瓣环速度。通过液相色谱串联质谱法测量了 Arg 衍生物的血浆浓度。在 143 名（70%）患有 DD 的患者中，ADMA 与 DD 的相关性最强（0.66±0.16、0.72±0.24 和 0.76±0.26µmol/L，趋势比较均<0.01）。在线性回归分析中，ADMA 每增加一个标准差，E 波（β系数（95%置信区间）：4.72（0.43-9.01）；<0.05）和平均 E/E'（1.76（0.73-2.79）<0.001）均呈正相关。调整了年龄、性别、体重指数（BMI）、糖尿病、冠状动脉疾病和高血压的因素。ADMA 升高与 HCM 中 DD 的严重程度相关。较高的 ADMA 水平可能导致 NO 生成减少，从而导致心肌舒张模式受损。
