大量临床数据显示，血液中炎症相关因子-脂蛋白相关磷脂酶A2（Lp-PLA2）水平与心血管疾病发生风险成正相关。在本课题组前期制备的Lp-PLA2转基因猪中，甘油三酯显著升高，LDL胆固醇升高。而脂质代谢紊乱正是心血管疾病最重要的致病因素，但目前尚未见Lp-PLA2升高与血脂浓度关系的相关研究。因此，拟进行如下研究：体外，以细胞系和原代细胞为载体，通过分子和细胞生物学技术，研究Lp-PLA2升高对脂质代谢相关基因的调节，分子机制及主要信号通路；体内，以Lp-PLA2转基因猪为载体，通过饮食干预，组织和分子生物学技术，研究Lp-PLA2升高对血液中TG清除及其水解酶的影响，研究Lp-PLA2升高对饮食干预后TC，HDL-C，LDL-C和TG水平的影响，在组织水平验证细胞水平实验。本研究将直观阐明Lp-PLA2升高对血脂水平的影响，为重新研究以其为靶点治疗心血管相关疾病提供理论依据。

Numbers of clinical data indicates that the pro-inflammatory factor Lp-PLA2 have positive relationship with cardiovascular disease (CVD). We have developed Lp-PLA2 transgenic pigs for related research previously. And triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) increased significantly in transgenic pigs’ blood. As well known that lipid metabolism dysfunction is one of the main factors of CVD, thus, Lp-PLA2 maybe have effects on lipid and cholesterol level and no related research was report currently. The project will processed according to the following design: In vitro, we will investigate the effects of Lp-PLA2 on related genes, mechanisms and main signaling pathway involved in cholesterol metabolism via molecular and cellular technology. And the research will done in cells; In vivo, we will investigate the effects of Lp-PLA2 on TG and the LPL activity after fat load and on TC, HDL-C, LDL-C and TG level after high fat diet intake in 6 months. We also verified the results of cells in Lp-PLA2 transgenic and non-transgenic pigs. And the research will done in pigs via diet intervention, histochemistry and molecular technologies. The research will shown the effects of Lp-PLA2 on lipid in blood directly and supported the Lp-PLA2 targeted research in prevention of CVD in second times.