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[鞘脂类在动脉粥样硬化发病机制中的作用]

[Participation of Sphingolipids in the Pathogenesis of Atherosclerosis].

作者信息

Alessenko A V, Zateyshchikov D A, Lebedev A Т, Kurochkin I N

机构信息

N.M. Emanuel Institute of Biochemical Physics.

City Clinical Hospital № 51; Central State Medical Academy of Department of Presidential Affairs.

出版信息

Kardiologiia. 2019 Aug 8;59(8):77-87. doi: 10.18087/cardio.2019.8.10270.

Abstract

Lipid metabolism disorders are the most significant risk factor of development of cardiovascular diseases (CVD). In the process of diagnosing ischemic heart disease and other cardiovascular pathologies, levels of total cholesterol, low- and high- density lipoprotein cholesterol, triglycerides are determined. However, in recent years, close attention has been paid to the intersection of the metabolic pathways of the biosynthesis of cholesterol and sphingolipids. Sphingolipids - a group of lipids, which include a molecule of aliphatic alcohol sphingosine. This group includes sphingomyelins, cerebrosides, gangliosides and ceramides, sphingosines and sphingosine-1-phosphate (S-1-P). Ceramides and sphingosines have pro-apoptotic properties, and S-1-P protects cells from apoptosis. Particular attention as inducer CVD attracts ceramide. It has been established that aggregated lipoproteins isolated from atherosclerotic zones are enriched with ceramides. The level of ceramide and sphingosine increases with ischemia/reperfusion of the heart, in the infarction zone and in the blood, and also in hypertensive disease. S-1-P has a pronounced cardioprotective properties. Its content sharply decreases with ischemia and myocardial infarction. S-1-P performs a special function in the structure of high-density lipoproteins (HDL), being one of the main lipid components of these lipoproteins, which determines their multiple functions. Recently, work has been underway to create drugs that can correct the metabolism of S-1-P. The most successful drugs are those that use the S-1-P receptor as a target, since all of its actions are carried out through receptors. Increasing ceramide and sphingosine and reducing blood plasma level of S-1-P can be an important factor in the development of atherosclerosis. It is proposed to use the determination of the level of sphingolipids in blood plasma for early diagnosis of cardiac ischemia and in arterial hypertension. Chromatography-mass spectrometry has been suggested as the main method for testing these lipids.

摘要

脂质代谢紊乱是心血管疾病(CVD)发生发展的最重要危险因素。在诊断缺血性心脏病和其他心血管疾病的过程中,需要测定总胆固醇、低密度和高密度脂蛋白胆固醇、甘油三酯的水平。然而,近年来,胆固醇和鞘脂生物合成代谢途径的交叉点受到了密切关注。鞘脂是一类脂质,其中包括脂肪醇鞘氨醇分子。该类包括鞘磷脂、脑苷脂、神经节苷脂和神经酰胺、鞘氨醇和鞘氨醇-1-磷酸(S-1-P)。神经酰胺和鞘氨醇具有促凋亡特性,而S-1-P可保护细胞免于凋亡。作为CVD的诱导剂,神经酰胺尤其受到关注。已经确定,从动脉粥样硬化区域分离出的聚集脂蛋白富含神经酰胺。心脏缺血/再灌注时、梗死区域和血液中以及高血压疾病中,神经酰胺和鞘氨醇的水平都会升高。S-1-P具有显著的心脏保护特性。其含量在缺血和心肌梗死时会急剧下降。S-1-P在高密度脂蛋白(HDL)的结构中发挥特殊作用,是这些脂蛋白的主要脂质成分之一,决定了它们的多种功能。最近,人们一直在致力于研发能够纠正S-1-P代谢的药物。最成功的药物是以S-1-P受体为靶点的药物,因为其所有作用都是通过受体实现的。神经酰胺和鞘氨醇增加以及血浆S-1-P水平降低可能是动脉粥样硬化发生发展的重要因素。有人建议将测定血浆中鞘脂水平用于心脏缺血和动脉高血压的早期诊断。色谱-质谱法已被建议作为检测这些脂质的主要方法。

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