Prasad Kailash
Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, Saskatchewan, Saskatoon, Canada.
Int J Angiol. 2020 Jun;29(2):72-80. doi: 10.1055/s-0039-3400541. Epub 2019 Dec 9.
Atrial fibrillation (AF) is the most common of cardiac arrhythmias. Mechanisms such as atrial structural remodeling and electrical remodeling have been implicated in the pathogenesis of AF. The data to date suggest that advanced glycation end products (AGEs) and its cell receptor RAGE (receptor for AGE) and soluble receptor (sRAGE) are involved in the pathogenesis of AF. This review focuses on the role of AGE-RAGE axis in the pathogenesis of AF. Interaction of AGE with RAGE generates reactive oxygen species, cytokines, and vascular cell adhesion molecules. sRAGE is a cytoprotective agent. The data show that serum levels of AGE and sRAGE, and expression of RAGE, are elevated in AF patients. Elevated levels of sRAGE did not protect the development of AF. This might be due to greater elevation of AGE than sRAGE. Measurement of AGE-RAGE stress (AGE/sRAGE) would be appropriate as compared with measurement of AGE or RAGE or sRAGE alone in AF patients. AGE and its interaction with RAGE can induce AF through alteration in cellular protein and extracellular matrix. AGE and its interaction with RAGE induce atrial structural and electrical remodeling. The treatment strategy should be directed toward reduction in AGE levels, suppression of RAGE expression, blocking of binding of AGE to RAGE, and elevation of sRAGE and antioxidants. In conclusion, AGE-RAGE axis is involved in the development of AF through atrial structural and electrical remodeling. The treatment modalities for AF should include lowering of AGE, suppression of RAGE, elevation of sRAGE, and use of antioxidants.
心房颤动（AF）是最常见的心律失常。心房结构重塑和电重塑等机制与AF的发病机制有关。迄今为止的数据表明，晚期糖基化终产物（AGEs）及其细胞受体RAGE（AGE受体）和可溶性受体（sRAGE）参与了AF的发病机制。本综述重点关注AGE-RAGE轴在AF发病机制中的作用。AGE与RAGE的相互作用会产生活性氧、细胞因子和血管细胞粘附分子。sRAGE是一种细胞保护剂。数据显示，AF患者血清中AGE和sRAGE水平以及RAGE表达均升高。sRAGE水平升高并不能保护AF的发生发展。这可能是由于AGE升高的幅度大于sRAGE。与单独测量AF患者的AGE、RAGE或sRAGE相比，测量AGE-RAGE应激（AGE/sRAGE）可能更合适。AGE及其与RAGE的相互作用可通过改变细胞蛋白和细胞外基质诱导AF。AGE及其与RAGE的相互作用可诱导心房结构和电重塑。治疗策略应旨在降低AGE水平、抑制RAGE表达、阻断AGE与RAGE的结合以及提高sRAGE和抗氧化剂水平。总之，AGE-RAGE轴通过心房结构和电重塑参与AF的发生发展。AF的治疗方式应包括降低AGE、抑制RAGE、提高sRAGE以及使用抗氧化剂。
