Research on advanced glycation end products in the mechanism of coronary artery disease

doi:10.3969/j.issn.1673-8640.2014.01.019

Abstract

Abstract: Advanced glycation end products (AGEs) are closely involved in the pathophysiological process of vascular smooth muscle cell (VSMCs) differentiation, proliferation, coronary artery disease and other cardiovascular diseases. AGEs can induce autophagy in VSMCs through the extracellular signal-regulated protein kinase(ERK) and serine-threonine kinase (Akt) signaling pathways. AGEs improve cardiac microvascular endothelial cell (CMECs) proliferation depending on bone marrow stromal cell-derived factor-1(SDF-1)/ chemokine receptor CXCR4 axis signaling pathway. AGEs-2 and AGEs-3 up-regulate the expression of receptor for advanced glycation end product (RAGE) on monocytes. AGEs inhibit the proliferation, migration and adhesion of endothelial progenitor cell (EPCs), and induce the apoptosis of EPCs. AGEs increase the expression activity of connective tissue growth factor(CTGF) mRNA and protein, and promote the proliferation of cardiac fibroblast and the secretion of transforming growth factor-beta 1 (TGF-β1) and induce the expressions of Smad2 and Smad4. The carboxymethyl lysine(CML)/RAGE axis plays an important role in atherosclerotic calcification of diabetes through the mechanism that induces the apoptosis of macrophages followed by the osteogenic differentiation of aortic smooth muscle cells. Soluble form of RAGE(sRAGE) can be served as bait of RAGE ligand to prevent atherosclerosis, and the sensitivity and negative predictive value of sRAGE are higher than those of AGEs/sRAGE ratio in identifying post-percutaneous coronary intervention (PCI) restenosis. ALT-711 is a breaker of AGEs-based cross links, which can inhibit AGEs-mediated formation of reactive oxygen species (ROS), extracellular signal-regulated kinase phosphorylation and cyclooxygenase-2 expression. Pigment epithelium-derived factor (PEDF) can inhibit CD40 ligand(CD40L) overexpression by blocking the effects of AGEs on platelets, which may become a therapeutic target for the prevention of coronary artery disease. Statins can also inhibit AGEs-induced aortic smooth muscle cell proliferation and production of ROS. The research above can reveal some the pathogenesis of coronary artery disease, provide foundation and direction for exploring the corresponding drug intervention and adjustment of clinical treatment strategies.

Key words: Advanced glycation end product, Receptor for advanced glycation end product, Coronary artery disease, Atherosclerosis, Vascular smooth muscle cell, Signal transduction

CLC Number:

R446.1

LIU Junfeng, KONG Meijuan, JIA Kegang.. Research on advanced glycation end products in the mechanism of coronary artery disease[J]. , 2014, 29(1): 76-80.

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