Hong Oak-Kee, Yoo Soon-Jib, Son Jang-Won, Kim Mee-Kyoung, Baek Ki-Hyun, Song Ki-Ho, Cha Bong-Yun, Jo Hanjoong, Kwon Hyuk-Sang
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.; Division of Endocrinology and Metabolism, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Kyunggi-do 14647, Korea.
Korean J Physiol Pharmacol. 2016 Mar;20(2):169-75. doi: 10.4196/kjpp.2016.20.2.169. Epub 2016 Feb 23.
Here, we investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) aff ect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this eff ect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a proinflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of infl ammatory adhesion molecules and ROS production. Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL.
在此,我们研究了高血糖和/或游离脂肪酸(棕榈酸,PAL)是否会影响内皮细胞中促动脉粥样硬化标志物骨形态发生蛋白4(BMP4)的表达水平,以及BMP4在糖尿病血管并发症中的潜在作用。为了测量BMP4的表达,将人脐静脉内皮细胞(HUVECs)暴露于高葡萄糖浓度和/或PAL中24或72小时,并检测这些处理对黏附分子和活性氧(ROS)表达水平的影响。通过转染BMP4特异性siRNA实现BMP4功能丧失状态。高糖水平以剂量依赖方式增加HUVECs中BMP4的表达。PAL增强了这种表达。高糖和/或PAL处理后,黏附分子水平和ROS产生增加,但当通过siRNA敲低BMP4时,这种作用被消除。高血糖和PAL增加了促炎和促动脉粥样硬化细胞因子标志物BMP4的信号传导。BMP4诱导炎症黏附分子的表达和ROS的产生。我们的研究表明,BMP4在高糖水平和/或PAL诱导的动脉粥样硬化中起作用。