Prasad Kailash
Department of Physiology (APP), College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Int J Angiol. 2021 Mar;30(1):4-14. doi: 10.1055/s-0040-1721813. Epub 2021 Jan 21.
Coronary artery atherosclerosis and atherosclerotic plaque rupture cause coronary artery disease (CAD). Advanced glycation end products (AGE) and its cell receptor RAGE, and soluble receptor (sRAGE) and endogenous secretory RAGE (esRAGE) may be involved in the development of atherosclerosis. AGE and its interaction with RAGE are atherogenic, while sRAGE and esRAGE have antiatherogenic effects. AGE-RAGE stress is a ratio of AGE/sRAGE. A high AGE-RAGE stress results in development and progression of CAD and vice-versa. AGE levels in serum and skin, AGE/sRAGE in patients with CAD, and expression of RAGE in animal model of atherosclerosis were higher, while serum levels of esRAGE were lower in patients with CAD compared with controls. Serum levels of sRAGE in CAD patients were contradictory, increased or decreased. This contradictory data may be due to type of patients used, because the sRAGE levels are elevated in diabetics and end-stage renal disease. AGE/sRAGE ratio is elevated in patients with reduced or elevated levels of serum sRAGE. It is to stress that AGE, RAGE, sRAGE, or esRAGE individually cannot serve as universal biomarker. AGE and sRAGE should be measured simultaneously to assess the AGE-RAGE stress. The treatment of CAD should be targeted at reduction in AGE levels, prevention of AGE formation, degradation of AGE in vivo, suppression of RAGE expression, blockade of RAGE, elevation of sRAGE, and use of antioxidants. In conclusion, AGE-RAGE stress would initiate the development and progression of atherosclerosis. Treatment modalities would prevent, regress, and slow the progression of CAD.
冠状动脉粥样硬化和动脉粥样硬化斑块破裂会导致冠状动脉疾病（CAD）。晚期糖基化终末产物（AGE）及其细胞受体RAGE、可溶性受体（sRAGE）和内源性分泌型RAGE（esRAGE）可能参与动脉粥样硬化的发展。AGE及其与RAGE的相互作用具有致动脉粥样硬化作用，而sRAGE和esRAGE具有抗动脉粥样硬化作用。AGE-RAGE应激是AGE与sRAGE的比值。高AGE-RAGE应激会导致CAD的发生和进展，反之亦然。与对照组相比，CAD患者血清和皮肤中的AGE水平、CAD患者的AGE/sRAGE以及动脉粥样硬化动物模型中RAGE的表达较高，而CAD患者的血清esRAGE水平较低。CAD患者的血清sRAGE水平存在矛盾，升高或降低。这种矛盾的数据可能是由于所使用的患者类型，因为糖尿病患者和终末期肾病患者的sRAGE水平会升高。血清sRAGE水平降低或升高的患者中AGE/sRAGE比值升高。需要强调的是，AGE、RAGE、sRAGE或esRAGE单独都不能作为通用的生物标志物。应同时测量AGE和sRAGE以评估AGE-RAGE应激。CAD的治疗应旨在降低AGE水平、预防AGE形成、体内AGE降解、抑制RAGE表达、阻断RAGE、升高sRAGE以及使用抗氧化剂。总之，AGE-RAGE应激会引发动脉粥样硬化的发生和进展。治疗方式将预防、逆转并减缓CAD的进展。
