Diminished global arginine bioavailability and increased arginine catabolism as metabolic profile of increased cardiovascular risk.
Diminished global arginine bioavailability and increased arginine catabolism as metabolic profile of increased cardiovascular risk.
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DOI：
10.1016/j.jacc.2009.02.036
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发表时间：
2009-06-02
影响因子：
24
通讯作者：
Hazen, Stanley L.
中科院分区：
文献类型：
--
作者：
Tang, W. H. Wilson;Wang, Zeneng;Cho, Leslie;Brennan, Danielle M.;Hazen, Stanley L.
我们假设精氨酸及其分解代谢产物的综合评估可能比单独精氨酸水平更好地预测心血管风险。精氨酸是一氧化氮（NO）合成的唯一氮源。精氨酸的主要分解代谢产物是鸟氨酸和瓜氨酸。采用LC/MS/MS测定血浆中游离精氨酸、鸟氨酸、瓜氨酸和内源性NO合成酶抑制剂不对称二甲基精氨酸（ADMA）的水平。（GABR，定义为精氨酸/[鸟氨酸+瓜氨酸]）对比精氨酸及其分解代谢产物与冠状动脉疾病（CAD）患病率和主要心血管不良事件发生率的关系（MACE =死亡、心肌梗死、卒中），对1,010例接受择期心导管插入术的受试者进行了3年随访。CAD患者的GABR [中位数（IQR）; 1.06（0.75，1.31）vs. 1.27（0.96，1.73），p<0.001]和精氨酸水平[平均值：68 ±20 μM vs. 74 ±24 μM，p<0.001]显著低于非CAD患者。在校正了脆性风险评分、C反应蛋白和肾功能后，精氨酸水平（而非精氨酸水平）和较高的瓜氨酸水平与CAD患病率[校正的比值比（OR）分别为3.93，p<0.001和5.98，p<0.001]和MACE发生率的3年风险[校正的风险比（HR）为1.98，分别为p=0.025和2.40，p=0.01]，并且在调整ADMA后仍具有显著性。与全身精氨酸水平相比，GABR可能是一个更全面的NO合成能力降低的概念。GABR降低和瓜氨酸水平升高与动脉粥样硬化性CAD的发生和主要不良心脏事件的长期风险升高相关。
We hypothesized that an integrated assessment of arginine with its catabolic products may better predict cardiovascular risks than arginine levels alone. Arginine is the sole nitrogen source for nitric oxide (NO) synthesis. The major catabolic products of arginine are ornithine and citrulline. Plasma levels of free arginine, ornithine, citrulline and the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) were measured using LC/MS/MS. We examined the relationship of global arginine bioavailability ratio (GABR, defined as arginine/[ornithine+citrulline]) vs. arginine and its catabolic metabolites to prevalence of coronary artery disease (CAD) and incidence of major adverse cardiovascular events (MACE = death, myocardial infarction, stroke) over a 3-year follow-up in 1,010 subjects undergoing elective cardiac catheterization. Patients with CAD had significantly lower GABR [median(IQR); 1.06(0.75, 1.31) versus 1.27(0.96, 1.73), p<0.001] and arginine levels [mean: 68 ±20 μM versus 74 ±24 μM, p<0.001) than those without CAD. After adjusting for Framingham risk score, C-reactive protein, and renal function, lower GABR (but not arginine levels) and higher citrulline levels remained significantly associated with both prevalence of CAD [adjusted odds-ratio (OR) 3.93, p<0.001 and 5.98, p<0.001, respectively] and 3-year risk for incidence of MACE [adjusted Hazard ratio (HR) 1.98, p=0.025 and 2.40, p=0.01, respectively], and remained significant after adjusting for ADMA. GABR may serve as a more comprehensive concept of reduced NO synthetic capacity compared to systemic arginine levels. Diminished GABR and high citrulline levels are associated with both development of atherosclerotic CAD and heightened long-term risk for major adverse cardiac events.
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DOI：
10.1073/pnas.0631696100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Lee, J;Chuang, TH;Cottam, HB
通讯作者：
Cottam, HB
影响因子：
4
作者：
Dumont, Julie;Zureik, Mahmoud;Brousseau, Thierry
通讯作者：
Brousseau, Thierry
影响因子：
3.5
作者：
Morris, SM
通讯作者：
Morris, SM
影响因子：
4.8
作者：
Schulze, Friedrich;Lenzen, Henrike;Boeger, Rainer H.
通讯作者：
Boeger, Rainer H.
影响因子：
37.8
作者：
Kielstein, JT;Impraim, B;Fliser, D
通讯作者：
Fliser, D