Circulating levels of nitrated apolipoprotein A-I are increased in type 2 diabetic patients
Circulating levels of nitrated apolipoprotein A-I are increased in type 2 diabetic patients
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DOI：
10.1515/cclm.2005.104
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发表时间：
2005-01-01
影响因子：
6.8
通讯作者：
Gugliucci, AG
中科院分区：
文献类型：
--
作者：
Hermo, R;Mier, C;Gugliucci, AG
最近的研究表明，从人类动脉粥样硬化病变和患有冠状动脉疾病的患者血液中分离出的高密度脂蛋白 (HDL) 含有升高水平的 3-硝基酪氨酸和 3-氯酪氨酸。脂蛋白中较高的硝基酪氨酸含量与脂蛋白的胆固醇流出能力降低显着相关。由于加速动脉粥样硬化形成是糖尿病的一个关键并发症，并且亚硝化应激最近与糖尿病病理学有关，因此我们着手证明 2 型糖尿病患者中硝化载脂蛋白 A (apoA)-I 循环水平的增加及其与代谢生物标志物的假定相关性。在这项工作中，我们通过一项病例对照研究解决了这一假设，该研究涉及 30 名 2 型糖尿病患者和 30 名年龄匹配的对照受试者。糖尿病患者的硝化 apoA-I 吸光度峰面积/apoA-1 (g/L) 为 3280 1910，对照受试者为 2320 890 (p < 0.037)。这表明，与年龄匹配的对照相比，糖尿病患者的循环硝化 apoA-I 增加了 50%。糖尿病患者的循环晚期糖基化终产物（以戊糖苷荧光测量）（44.16 +/- 16.26 vs. 30.84 +/- 12.86 AU；p < 0.01）和循环脂过氧化物（46.0 +/- 18.0 vs. 37.2 +/- 18.0 nmol/L；p < 0.03）也显示出类似幅度的增加。 apoA-1 的硝化与糖基化血红蛋白或任何其他测量参数之间没有发现显着相关性。如果在随后的功能和体内研究中得到证实，硝化 apoA-I 的增加将代表亚硝化应激参与糖尿病大血管病变的另一种机制。
Recent work has shown that high-density lipoprotein (HDL) isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels of 3-nitrotyrosine and 3-chlorotyrosine. A higher nitrotyrosine content in lipoprotein is significantly associated with diminished cholesterol efflux capacity of the lipoprotein. Since accelerated atherogenesis is a key complication of diabetes mellitus, and nitrosative stress has recently been implicated in diabetic pathology, we set out to demonstrate an increase in the circulating levels of nitrated apolipoprotein A (apoA)-I in type 2 diabetic patients and its putative correlation with metabolic biomarkers. In this work we addressed this hypothesis in a case-control study with 30 type 2 diabetic patients and 30 age-matched control subjects. Nitrated apoA-I was 3280 1910 absorbance peak area/apoA-1 (g/L) for diabetic patients and 2320 890 for control subjects (p < 0.037). This represents a 50% increase in circulating nitrated apoA-I in diabetic patients to age-matched controls. Diabetic patients also showed increases of a similar magnitude in circulating advanced glycation endproducts measured as pentosidine fluorescence (44.16 +/- 16.26 vs. 30.84 +/- 12.86 AU; p < 0.01) and in circulating lipoperoxides (46.0 +/- 18.0 vs. 37.2 +/- 18.0 nmol/L; p < 0.03). No significant correlation was found between nitration of apoA-1 and glycosylated hemoglobin or any of the other parameters measured. If proven in subsequent functional and in vivo studies, increased nitrated apoA-I would represent another mechanism by which nitrosative stress participates in diabetic macroangiopathy.