Lankin Vadim Z, Tikhaze Alla K, Melkumyants Arthur M
Department for Free Radical Research, National Medical Research Center of Cardiology Russian Ministry of Health, 121552 Moscow, Russia.
Antioxidants (Basel). 2022 Aug 12;11(8):1565. doi: 10.3390/antiox11081565.
The review presents evidence that the main damage to the vascular wall occurs not from the action of "oxidized" LDL, which contain hydroperoxy acyls in the phospholipids located in their outer layer, but from the action of LDL particles whose apoprotein B-100 is chemically modified with low molecular weight dicarbonyls, such as malondialdehyde, glyoxal, and methylglyoxal. It has been argued that dicarbonyl-modified LDL, which have the highest cholesterol content, are particularly "atherogenic". High levels of dicarbonyl-modified LDL have been found to be characteristic of some mutations of apoprotein B-100. Based on the reviewed data, we hypothesized a common molecular mechanism underlying vascular wall damage in atherosclerosis and diabetes mellitus. The important role of oxidatively modified LDL in endothelial dysfunction is discussed in detail. In particular, the role of the interaction of the endothelial receptor LOX-1 with oxidatively modified LDL, which leads to the expression of NADPH oxidase, which in turn generates superoxide anion radical, is discussed. Such hyperproduction of ROS can cause destruction of the glycocalyx, a protective layer of endotheliocytes, and stimulation of apoptosis in these cells. On the whole, the accumulated evidence suggests that carbonyl modification of apoprotein B-100 of LDL is a key factor responsible for vascular wall damage leading to atherogenesis and endothelial dysfunction. Possible ways of pharmacological correction of free radical processes in atherogenesis and diabetogenesis are also discussed.
该综述提出的证据表明，血管壁的主要损伤并非源于“氧化”低密度脂蛋白（LDL）的作用，这类LDL在外层磷脂中含有氢过氧酰基，而是源于载脂蛋白B - 100经低分子量二羰基化合物（如丙二醛、乙二醛和甲基乙二醛）化学修饰的LDL颗粒的作用。有人认为，胆固醇含量最高的二羰基修饰LDL具有特别的“致动脉粥样硬化性”。已发现二羰基修饰LDL水平升高是载脂蛋白B - 100某些突变的特征。基于所综述的数据，我们推测动脉粥样硬化和糖尿病中血管壁损伤存在共同的分子机制。详细讨论了氧化修饰LDL在内皮功能障碍中的重要作用。特别是，讨论了内皮受体LOX - 1与氧化修饰LDL相互作用导致NADPH氧化酶表达的作用，NADPH氧化酶进而产生超氧阴离子自由基。这种活性氧的过度产生可导致内皮细胞保护层糖萼的破坏，并刺激这些细胞的凋亡。总体而言，积累的证据表明，LDL的载脂蛋白B - 100的羰基修饰是导致动脉粥样硬化和内皮功能障碍的血管壁损伤的关键因素。还讨论了动脉粥样硬化和糖尿病发生过程中自由基过程的药理学纠正的可能方法。
