摘要
晚期糖基化终产物(AGEs)密切参与了血管平滑肌细胞(VSMCs)分化与增殖以及冠心病等心血管疾病的病理生理过程。AGEs能通过单核细胞趋化蛋白(ERK)、丝氨酸/苏氨酸蛋白激酶(Akt)信号通路来诱导VSMCs的自噬作用,可依赖骨髓基质细胞衍生因子-1(SDF-1)/趋化因子受体CXCR4轴信号通路促进心肌微血管内皮细胞(CMECs)的增生。AGEs-2和AGEs-3上调了单核细胞AGEs受体(RAGE)的表达。AGEs能抑制内皮祖细胞(EPCs)的增殖、迁移和黏附功能并诱导EPCs凋亡;能增加平滑肌细胞结缔组织因子(CTGF)mRNA和蛋白质的表达,刺激心肌成纤维细胞增殖并分泌转化生长因子-β1(TGF-β1),同时诱导Smad2及Smad4的表达。羧甲基赖氨酸(CML)/RAGE轴通过主动脉平滑肌成骨细胞的分化,诱导巨噬细胞凋亡,从而使AGEs在糖尿病动脉粥样硬化中发挥重要作用。可溶性RAGE(sRAGE)可作为RAGE配体的诱饵来防止动脉粥样硬化,其灵敏度和阴性预测值在判定冠状动脉介入治疗(PCI)术后再狭窄方面均高于AGEs/sRAGE比值。ALT-711是一种AGEs的裂解剂,能明显抑制AGEs介导的活性氧(ROS)产生、细胞外信号调节激酶磷酸化及环氧合酶-2的表达;色素上皮衍生因子(PEDF)能抑制AGEs诱导的血小板CD40配体(CD40L)表达,从而有可能成为预防冠心病的一个治疗靶点。他汀类药物亦能抑制AGEs诱导主动脉平滑肌细胞的增殖及ROS的产生。通过以上诸多因素的研究,可揭示冠心病的某些发病机制,为相应干预药物的研究及调整临床治疗策略提供依据和方向。
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 CIM0 ligand (CIMOL) 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.
出处
《检验医学》
CAS
2014年第1期76-80,共5页
Laboratory Medicine
关键词
晚期糖基化终产物
晚期糖基化终产物受体
冠心病
动脉粥样硬化
血管平滑肌细胞
信号传导
Advanced glycation end product
Receptor for advanced glycation end product
Coronary arterydisease
Atherosclerosis
Vascular smooth muscle cell
Signal transduction