愤怒(情绪)
糖基化
医学
受体
糖基化终产物
细胞粘附分子
HMGB1
炎症
信号转导
免疫学
内分泌学
内科学
细胞生物学
生物
神经科学
作者
Kei Fukami,Sho‐ichi Yamagishi,Seiya Okuda
标识
DOI:10.2174/13816128113199990475
摘要
Advanced glycation end products (AGEs) are a heterogenous group of molecules formed during a non-enzymatic reaction between proteins and sugar residues. Recently, AGEs and their receptor (receptor for AGEs; RAGE) play a central role in the pathogenesis of cardiovascular disease (CVD), which accounts for disability and high mortality rate in patients with diabetes. AGEs initiate diabetic micro- and macrovascular complications through the structural modification and functional alteration of the extracellular matrix proteins as well as intracellular signaling molecules. Engagement of RAGEs with AGEs elicits intracellular reactive oxygen species (ROS) generation and subsequently activates mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling, followed by production of several inflammatory and/or profibrotic factors such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), plasminogen activator inhibitor-1 (PAI-1) and monocyte chemoattractant protein-1 (MCP-1), thereby being involved in the progression of atherosclerosis. Administration of soluble form of RAGE (sRAGE) could work as a decoy receptor for AGEs and might inhibit the binding of AGEs to RAGE, preventing the development and progression of atherosclerosis in animal models. Furthermore, AGEs/high mobility group box-1 (HMGB-1)-RAGE interaction is involved in heart failure, abdominal aortic aneurysm (AAA) and vascular calcification as well. Thus, blockade of the AGEs/HMGB-1-RAGE system may be a promising therapeutic target for preventing diabetes- and/or age-related CVD. We review here the pathological role of the AGEs/HMGB-1-RAGE system in various types of CVD. Keywords: RAGE, AGEs, cardiovascular disease, oxidative stress, HMGB-1.
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