Zhou Yi Jun, Wang Jia He, Zhang Jin
Department of Endocrinology and Metabolism, First Affiliated Hospital, China Medical University, Shenyang 110001, PR China.
Biochem Biophys Res Commun. 2006 Jun 2;344(2):658-66. doi: 10.1016/j.bbrc.2006.03.167. Epub 2006 Apr 4.
Advanced glycation end products (AGEs) form by a non-enzymatic reaction between reducing sugars and biological proteins, which play an important role in the pathogenesis of atherosclerosis. In this study, we assessed AGEs effects on human umbilical vein endothelial cells (HUVECs) growth, proliferation and apoptosis. Additionally, we investigated whether hepatocyte growth factor (HGF), an anti-apoptotic factor for endothelial cells, prevents AGEs-induced apoptosis of HUVECs. HUVECs were treated with AGEs in the presence or absence of HGF. Treatment of HUVECs with AGEs changed cell morphology, decreased cell viability, and induced DNA fragmentation, leading to apoptosis. Apoptosis was induced by AGEs in a dose- and time-dependent fashion. AGEs markedly elevated Bax and decreased NF-kappaB, but not Bcl-2 expression. Additionally, AGEs significantly inhibited cell growth through a pro-apoptotic action involving caspase-3 and -9 activations in HUVECs. Most importantly, pretreatment with HGF protected against AGEs-induced cytotoxicity in the endothelial cells. HGF significantly promoted the expression of Bcl-2 and NF-kappaB, while decreasing the activities of caspase-3 and -9 without affecting Bax level. Our data suggest that AGEs induce apoptosis in endothelial cells. HGF effectively attenuate AGEs-induced endothelial cell apoptosis. These findings provide new perspectives in the role of HGF in cardiovascular disease.
晚期糖基化终末产物（AGEs）通过还原糖与生物蛋白质之间的非酶促反应形成，在动脉粥样硬化的发病机制中起重要作用。在本研究中，我们评估了AGEs对人脐静脉内皮细胞（HUVECs）生长、增殖和凋亡的影响。此外，我们研究了内皮细胞抗凋亡因子肝细胞生长因子（HGF）是否能预防AGEs诱导的HUVECs凋亡。在有或无HGF存在的情况下，用AGEs处理HUVECs。用AGEs处理HUVECs会改变细胞形态、降低细胞活力并诱导DNA片段化，从而导致细胞凋亡。AGEs以剂量和时间依赖性方式诱导细胞凋亡。AGEs显著升高Bax并降低NF-κB，但不影响Bcl-2表达。此外，AGEs通过涉及HUVECs中caspase-3和-9激活的促凋亡作用显著抑制细胞生长。最重要的是，用HGF预处理可保护内皮细胞免受AGEs诱导的细胞毒性。HGF显著促进Bcl-2和NF-κB的表达，同时降低caspase-3和-9的活性，而不影响Bax水平。我们的数据表明AGEs诱导内皮细胞凋亡。HGF有效减轻AGEs诱导的内皮细胞凋亡。这些发现为HGF在心血管疾病中的作用提供了新的视角。
