Russian Cardiology Research and Production Complex, Ministry of Healthcare of Russian Federation, 3rd Cherepkovskaya St. 15a, Moscow 121552, Russia.
Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky Ave., 27, Moscow 119192, Russia.
Oxid Med Cell Longev. 2017;2017:1625130. doi: 10.1155/2017/1625130. Epub 2017 Oct 2.
Malondialdehyde (MDA), glyoxal (GO), and methylglyoxal (MGO) levels increase in atherosclerosis and diabetes patients. Recent reports demonstrate that GO and MGO cause vascular endothelial barrier dysfunction whereas no evidence is available for MDA.
To compare the effects of MDA, GO, or MGO on endothelial permeability, we used human EA.hy926 endothelial cells as a standard model. To study cortical cytoplasm motility and cytoskeletal organization in endothelial cells, we utilized time-lapse microscopy and fluorescent microscopy. To compare dicarbonyl-modified protein band profiles in these cells, we applied Western blotting with antibodies against MDA- or MGO-labelled proteins.
MDA (150-250 M) irreversibly suppressed the endothelial cell barrier, reduced lamellipodial activity, and prevented intercellular contact formation. The motile deficiency of MDA-challenged cells was accompanied by alterations in microtubule and microfilament organization. These detrimental effects were not observed after GO or MGO (250 M) administration regardless of confirmed modification of cellular proteins by MGO.
Our comparative study demonstrates that MDA is more damaging to the endothelial barrier than GO or MGO. Considering that MDA endogenous levels exceed those of GO or MGO and tend to increase further during lipoperoxidation, it appears important to reduce oxidative stress and, in particular, MDA levels in order to prevent sustained vascular hyperpermeability in atherosclerosis and diabetes patients.
丙二醛（MDA）、乙二醛（GO）和甲基乙二醛（MGO）水平在动脉粥样硬化和糖尿病患者中升高。最近的报告表明 GO 和 MGO 会导致血管内皮屏障功能障碍，而 MDA 是否会导致这种情况尚无证据。
为了比较 MDA、GO 或 MGO 对内皮通透性的影响，我们使用人 EA.hy926 内皮细胞作为标准模型。为了研究内皮细胞皮质细胞质运动和细胞骨架组织，我们利用延时显微镜和荧光显微镜。为了比较这些细胞中双羰基修饰蛋白条带的特征，我们应用了针对 MDA 或 MGO 标记蛋白的 Western blot 分析。
MDA（150-250μM）不可逆地抑制内皮细胞屏障，降低片状伪足活性，并阻止细胞间接触的形成。MDA 挑战细胞的运动缺陷伴随着微管和微丝组织的改变。在用 GO 或 MGO（250μM）处理后，没有观察到这些有害影响，无论 MGO 是否确实修饰了细胞蛋白。
我们的比较研究表明，MDA 对内皮屏障的破坏作用大于 GO 或 MGO。考虑到 MDA 的内源性水平超过 GO 或 MGO，并且在脂质过氧化过程中趋于进一步增加，因此降低氧化应激，特别是 MDA 水平，以防止动脉粥样硬化和糖尿病患者的血管持续高通透性似乎很重要。
