GAPDH AND ITS PROTECTIVE ROLE IN ATHEROSCLEROSIS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 能量产生不足、DNA修复受损和平滑肌细胞（SMC）凋亡是晚期动脉粥样硬化斑块的标志。甘油醛-3-磷酸脱氢酶（GAPDH）是一种多功能糖酵解酶，在能量生产中起着重要作用。GAPDH还保护细胞基因组的完整性，并且氧化应激修饰的GAPDH启动细胞凋亡。该项目的主要假设是，在SMC中恢复GAPDH水平将在体外对氧化剂诱导的细胞凋亡和细胞迁移的抑制以及在体内对饮食诱导的动脉粥样硬化具有保护作用。 我们将确定在有/没有氧化剂的情况下操纵SMC中的GAPDH水平是否会转化为细胞迁移和细胞凋亡的充分变化。由于进行性DNA损伤与动脉粥样硬化进展相关，我们计划研究GAPDH是否在氧化剂诱导的SMC DNA损伤中起保护作用。我们还计划测试恢复动脉粥样硬化SMC中GAPDH水平是否会刺激细胞能量产生并导致动脉粥样硬化减少。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Insufficient energy production, impaired DNA repairing and smooth muscle cell (SMC) apoptosis are hallmarks of advanced atherosclerotic plaque. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional glycolytic enzyme that plays an important role in energy production. GAPDH also protects the cell genome integrity and oxidative stress-modified GAPDH initiates the cell apoptosis. The major hypothesis of this project that restoring GAPDH levels in SMC would be protective against oxidant-induced apoptosis and suppression of cell migration in vitro and against diet-induced atherosclerosis in vivo. We will determine if manipulation of GAPDH levels in SMC with/without oxidant would be translated into adequate changes in cell migration and apoptosis. Since progressive DNA damage is associated with atherosclerosis progression, we plan to study if GAPDH plays a protective role in oxidant-induced DNA damage in SMC. We also plan to test if restoring GAPDH levels in atherosclerotic SMC would stimulate cell energy production and leads to a reduction in atherosclerosis.