Prasad Kailash, Khan Amal S, Bhanumathy Kalpana K
Department of Physiology (APP), College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Community, Health and Epidemiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Int J Angiol. 2022 Feb 12;31(1):1-9. doi: 10.1055/s-0042-1742587. eCollection 2022 Mar.
This article deals with the role of AGE (advanced glycation end products)-RAGE (receptor for AGE) stress (AGE/sRAGE) in the development of coronary artery disease (CAD) in obesity. CAD is due to atherosclerosis in coronary artery. The serum/plasma levels of AGE and sRAGE are reduced, while AGE-RAGE stress and expression of RAGE are elevated in obese individuals. However, the levels of AGE are elevated in obese individuals with more than one metabolic syndrome. The increases in the AGE-RAGE stress would elevate the expression and production of atherogenic factors, including reactive oxygen species, nuclear factor-kappa B, cytokines, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial leukocyte adhesion molecules, monocyte chemoattractant protein-1, granulocyte-macrophage colony-stimulating factor, and growth factors. Low levels of sRAGE would also increase the atherogenic factors. The increases in the AGE-RAGE stress and decreases in the levels of sRAGE would induce development of atherosclerosis, leading to CAD. The therapeutic regimen for AGE-RAGE stress-induced CAD in obesity would include lowering of AGE intake, prevention of AGE formation, degradation of AGE in vivo, suppression of RAGE expression, blockade of AGE-RAGE interaction, downregulation of sRAGE expression, and use of antioxidants. In conclusion, the data suggest that AGE-RAGE stress is involved in the development of CAD in obesity, and the therapeutic interventions to reduce AGE-RAGE would be helpful in preventing, regressing, and slowing the progression of CAD in obesity.
本文探讨了晚期糖基化终末产物（AGE）-晚期糖基化终末产物受体（RAGE）应激（AGE/sRAGE）在肥胖人群冠状动脉疾病（CAD）发生发展中的作用。CAD是由冠状动脉粥样硬化引起的。肥胖个体血清/血浆中AGE和可溶性RAGE（sRAGE）水平降低，而AGE-RAGE应激及RAGE表达升高。然而，患有不止一种代谢综合征的肥胖个体中AGE水平升高。AGE-RAGE应激增加会提高包括活性氧、核因子κB、细胞因子、细胞间黏附分子-1、血管细胞黏附分子-1、内皮白细胞黏附分子、单核细胞趋化蛋白-1、粒细胞-巨噬细胞集落刺激因子和生长因子等致动脉粥样硬化因子的表达和产生。低水平的sRAGE也会增加致动脉粥样硬化因子。AGE-RAGE应激增加和sRAGE水平降低会诱发动脉粥样硬化的发展，导致CAD。针对肥胖人群中AGE-RAGE应激诱导的CAD的治疗方案包括降低AGE摄入、预防AGE形成、体内AGE降解、抑制RAGE表达、阻断AGE-RAGE相互作用、下调sRAGE表达以及使用抗氧化剂。总之，数据表明AGE-RAGE应激参与了肥胖人群CAD的发生发展，减少AGE-RAGE的治疗干预措施有助于预防、消退和减缓肥胖人群CAD的进展。
