Enhancement of vascular vessels senescence caused by a fibrinolytic inhibitor, PAI-1.

为了探讨PAI-1在血管衰老中的作用，我们采用血管内皮细胞系UV♀-2细胞研究衰老的分子机制，并利用PAI-1 KO小鼠研究衰老与体内衰老的关系。融合后的UV♀2细胞增加了衰老相关的CDKI、p16^和lt；INK4A和GT；以及衰老标志物SA-β-GAL染色的表达水平。通过RNA干扰敲除PAI-1基因后，p16基因在这些细胞中的表达降低。白藜芦醇是一种在红葡萄酒中发现的抗氧化剂多酚，用白藜芦醇处理可以降低p16^&lt；Ink4a&gt；的表达水平和SA-β-Gal染色。用老年和年轻小鼠的主动脉RNA进行的DNA芯片分析表明，与年轻小鼠相比，衰老血管的PAI-1、MnSOD、HSP等基因的表达水平增加；与野生型小鼠相比，PAI-1 KO小鼠的衰老血管降低了与细胞骨架、细胞外基质和线粒体成分相关的基因的表达水平。

To investigate the role of PAI-1 in vascular vessels senescence, we employed a vascular endothelial cell line, UV♀2 cells, for studying molecular mechanisms of senescence and PAI-1 KO mice for studying the links between senescence and aging in vivo. After confluent, UV♀2 cells increased expression levels of senescence-associated CDKI, p16^<INK4A> and a senescence marker, SA-β-gal staining. PAI-1 knockdown by RNA interference results in reduction of p16^<INK4A> gene expression in these cells. Treatments with resveratrol, an antioxidant polyphenol found in red wine, reduced p16^<INK4A> expression levels and SA-β-gal staining. DNA microarray analysis using aorta RNA from old-aged and young mice revealed that aging blood vessels increased expression levels of genes, such as PAI-1, MnSOD, Hsp etc. compared with young one and that aging blood vessels form PAI-1 KO mice reduced expression levels of genes concerned with cytoskeleton, extracellular matrix, mitochondrial components as compared with that from wild-type mice.