Ba Jianming, Peng Hu, Chen Yanqing, Gao Yong
Emergency Department, Shanghai Tenth People's Hospital, Shanghai, 200072, China.
Cell Biochem Biophys. 2014 Dec;70(3):1533-8. doi: 10.1007/s12013-014-0089-z.
Atherosclerosis is the common pathological basis of cardiovascular and cerebrovascular disease. This study aimed to investigate the effects of vascular endothelial growth factor (VEGF) and salvianolic acid B (SalB) on the permeability of the rabbit aortary endothelial cells (RAECs) and to figure out the possible underlying molecular mechanisms. The extravasation of (125)I-low density lipoprotein ((125)I-LDL) through the RAECs was significantly increased by VEGF and decreased by SalB. Meanwhile, the tight junction-associated proteins occludin and claudin-5 were found downregulated by VEGF and the caveolae structure proteins caveolin-1 and caveolin-2 upregulated, which were abolished by the infusion of SalB. In addition, a marked increase in levels of cGMP and protein kinase G-1 (PKG-1) as well as activation of nuclear factor-κB (NF-κB) p65 were found after VEGF infusion, which were attenuated by SalB. This study demonstrates that VEGF and SalB can alter the LDL permeability of the RAECs by a paracellular pathway (downregulation of occludin and claudin-5) and a transcellular pathway (upregulation of caveolin-1 and caveolin-2), in which the cGMP/PKG/NF-κB signal pathway is possibly involved. The experimental results provide a new method and basic knowledge of prevention and treatment for cardiovascular and cerebrovascular disease.
动脉粥样硬化是心脑血管疾病的常见病理基础。本研究旨在探讨血管内皮生长因子（VEGF）和丹酚酸B（SalB）对兔主动脉内皮细胞（RAECs）通透性的影响，并找出可能的潜在分子机制。VEGF显著增加了（125）I-低密度脂蛋白（（125）I-LDL）通过RAECs的外渗，而SalB则使其减少。同时，发现紧密连接相关蛋白occludin和claudin-5被VEGF下调，小窝结构蛋白caveolin-1和caveolin-2上调，而SalB的注入消除了这些变化。此外，VEGF注入后发现cGMP和蛋白激酶G-1（PKG-1）水平显著升高以及核因子-κB（NF-κB）p65激活，而SalB使其减弱。本研究表明VEGF和SalB可通过细胞旁途径（occludin和claudin-5下调）和穿细胞途径（caveolin-1和caveolin-2上调）改变RAECs的LDL通透性，其中可能涉及cGMP/PKG/NF-κB信号通路。实验结果为心脑血管疾病的防治提供了新方法和基础知识。
