Objective To review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1） including its protein, ligands, expression and pathophysiological significance. Data sources Inform...Objective To review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1） including its protein, ligands, expression and pathophysiological significance. Data sources Information included in this article was identified by searching of PUBMED （1997-2006） online resources using the key term LOX-1. Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected. Results The key issues related to the LOX-1 protein as well as ligands for LOX-1. Factors regulating the expression of LOX-1 were summarized. The pathophysiological functions of LOX-1 in several diseases were discussed. Conclusions Identification of LOX-1 and a definition of its biological role in pathophysiologic states provide deeper insight into the pathogenesis of some cardiovascular diseases especially in atherosclerosis and provide a potential selective therapeutic approach. LOX-1 is unlocking and drugs targeting LOX-1 might be a promising direction to explore.展开更多
Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum （ER） stress related with atherosclerosis. Oxidized LDL （ox-LDL） also induces endothelial apoptosis and plays a vital role in th...Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum （ER） stress related with atherosclerosis. Oxidized LDL （ox-LDL） also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells （HUVECs） were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.展开更多
目的探讨冠心病患者幽门螺杆菌(Helicobacter pylori,HP)感染与血清中氧化低密度脂蛋白(oxidized low density lipoprotein,ox-LDL)水平及冠状动脉病变严重程度之间的关系。方法选取2012年12月-2013年11月在常德市第一人民医院行冠脉造...目的探讨冠心病患者幽门螺杆菌(Helicobacter pylori,HP)感染与血清中氧化低密度脂蛋白(oxidized low density lipoprotein,ox-LDL)水平及冠状动脉病变严重程度之间的关系。方法选取2012年12月-2013年11月在常德市第一人民医院行冠脉造影确诊为冠心病的患者159例作为研究对象。采用14C尿素呼气试验测定其HP感染状况,根据14C尿素呼气试验结果将所有受试者分为HP感染组和非HP感染组,同时采用酶联免疫吸附法测定其血清ox-LDL水平。结果冠心病患者HP感染组血清ox-LDL、TC、LDL、TG水平高于非HP感染组,差异均有统计学意义(P<0.05,P<0.01);不同HP感染程度分组患者血清ox-LDL水平差异有统计学意义(F=22.299,P<0.01),随着患者体内HP感染程度的加重,其血清ox-LDL水平相应增高;不同冠状动脉病变程度分组患者血清ox-LDL水平差异有统计学意义(F=8.711,P<0.01),血清ox-LDL水平随着冠状动脉病变严重程度增加而呈递增趋势。多元线性回归分析显示,HP感染以及血清ox-LDL、LDL、TC、TG、HDL-C均为冠心病患者冠状动脉Gensini评分的影响因素。结论 HP感染可能通过引起脂质代谢紊乱、升高血清ox-LDL水平来增加冠状动脉血管损害程度,从而在冠心病的发生发展中起着至关重要的作用。展开更多
文摘Objective To review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1） including its protein, ligands, expression and pathophysiological significance. Data sources Information included in this article was identified by searching of PUBMED （1997-2006） online resources using the key term LOX-1. Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected. Results The key issues related to the LOX-1 protein as well as ligands for LOX-1. Factors regulating the expression of LOX-1 were summarized. The pathophysiological functions of LOX-1 in several diseases were discussed. Conclusions Identification of LOX-1 and a definition of its biological role in pathophysiologic states provide deeper insight into the pathogenesis of some cardiovascular diseases especially in atherosclerosis and provide a potential selective therapeutic approach. LOX-1 is unlocking and drugs targeting LOX-1 might be a promising direction to explore.
基金State Key Clinical Specialty Construction Project,China
文摘Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum （ER） stress related with atherosclerosis. Oxidized LDL （ox-LDL） also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells （HUVECs） were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.
