Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress.
Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress.
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DOI：
10.1007/s00125-010-1677-0
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发表时间：
2010-05
期刊：
影响因子：
8.2
通讯作者：
Schalkwijk, C. G.
中科院分区：
文献类型：
--
作者：
Brouwers, O.;Niessen, P. M.;Haenen, G.;Miyata, T.;Brownlee, M.;Stehouwer, C. D.;De Mey, J. G.;Schalkwijk, C. G.
一氧化氮（NO）依赖性血管舒张功能受损在糖尿病血管并发症的发展中起着关键作用。我们研究了高脂血症对血管反应性受损的影响，以及AGE前体甲基乙二醛在其中的假定作用。高葡萄糖和甲基乙二醛对来自野生型和转基因glycoprotein酶（GLO）-I（也称为GLO 1）大鼠（即解毒甲基乙二醛的酶）的分离的大鼠肠系膜动脉中的NO依赖性血管舒张的影响记录在钢丝肌描记器中。用抗MG-H1的抗体检测主要甲基甘氨酸加合物5-氢-5-甲基咪唑酮（MG-H1）的AGE形成，并用超高效液相色谱（串联）质谱法定量。用5-（和-6）-氯甲基-2 ′7′-二氯二氢荧光素二乙酸乙酰酯探针和硝基酪氨酸抗体免疫组织化学法测定活性氧的形成。高糖和丙酮醛暴露使NO依赖性血管舒张作用显著降低（p < 0.05）。在GLO-I转基因大鼠的肠系膜动脉中未观察到这种损伤，表明特异性细胞内甲基乙二醛效应。GLO-I过表达可显著改善糖尿病诱导的野生型大鼠肠系膜动脉功能受损（pD 2）（p < 0.05）。甲基甘氨酸修饰的白蛋白不影响NO依赖性血管舒张，而在相同条件下，AGE配体S100 b的受体则影响NO依赖性血管舒张（p < 0.05）。甲基乙二醛治疗动脉增加了MG-H1在内皮细胞和外膜的细胞内染色的5倍，伴随着8倍的氧化应激标志物硝基酪氨酸的增加。抗氧化剂预孵育防止甲基甘氨酸诱导的血管反应性损伤。这些数据表明，高血压诱导的内皮依赖性血管舒张功能障碍是通过氧化应激途径中细胞内甲基乙二醛水平升高介导的。本文的在线版本（doi：10.1007/s 00125 -010-1677-0）包含补充材料，可供授权用户使用。
Impaired nitric oxide (NO)-dependent vasorelaxation plays a key role in the development of diabetic vascular complications. We investigated the effect of hyperglycaemia on impaired vasoreactivity and a putative role therein of the AGE precursor methylglyoxal. The effects of high glucose and methylglyoxal on NO-dependent vasorelaxation in isolated rat mesenteric arteries from wild-type and transgenic glyoxalase (GLO)-I (also known as GLO1) rats, i.e. the enzyme detoxifying methylglyoxal, were recorded in a wire myograph. AGE formation of the major methylglyoxal-adduct 5-hydro-5-methylimidazolone (MG-H1) was detected with an antibody against MG-H1 and quantified with ultra-performance liquid chromatography (tandem) mass spectrometry. Reactive oxygen species formation was measured with a 5-(and-6)-chloromethyl-2′7′-dichlorodihydrofluorescein diacetate acetyl ester probe and by immunohistochemistry with an antibody against nitrotyrosine. High glucose and methylglyoxal exposure of mesenteric arteries significantly reduced the efficacy of NO-dependent vasorelaxation (p < 0.05). This impairment was not observed in mesenteric arteries of GLO-I transgenic rats indicating a specific intracellular methylglyoxal effect. The diabetes-induced impaired potency (pD2) in mesenteric arteries of wild-type rats was significantly improved by GLO-I overexpression (p < 0.05). Methylglyoxal-modified albumin did not affect NO-dependent vasorelaxation, while under the same conditions the receptor for AGE ligand S100b did (p < 0.05). Methylglyoxal treatment of arteries increased intracellular staining of MG-H1 in endothelial cells and adventitia by fivefold accompanied by an eightfold increase in the oxidative stress marker nitrotyrosine. Antioxidant pre-incubation prevented methylglyoxal-induced impairment of vasoreactivity. These data show that hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation is mediated by increased intracellular methylglyoxal levels in a pathway dependent on oxidative stress. The online version of this article (doi:10.1007/s00125-010-1677-0) contains supplementary material, which is available to authorised users.
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影响因子：
--
作者：
DIEDERICH, D;SKOPEC, J;DAI, FX
通讯作者：
DAI, FX
影响因子：
16.2
作者：
Kilhovd, BK;Berg, TJ;Hanssen, KF
通讯作者：
Hanssen, KF
DOI：
10.1196/annals.1333.017
发表时间：
2005-01-01
期刊：
MAILLARD REACTION: CHEMISTRY AT THE INTERFACE OF NUTRITION, AGING, AND DISEASE
影响因子：
--
作者：
Lee, HJ;Howell, SK;Beisswenger, PJ
通讯作者：
Beisswenger, PJ
影响因子：
9.8
作者：
Fosmark, DS;Torjesen, PA;Agardh, E
通讯作者：
Agardh, E
影响因子：
8.2
作者：
Hammes, HP;Brownlee, M;Bretzel, RG
通讯作者：
Bretzel, RG