Pathobiochemical and immunological study on infection-accelerated atherosclerosis and its regulation.

在本研究中，我们研究了幽门螺杆菌感染在动脉粥样硬化易感模型(APOE^&lt；-/-&gt；LDLR^&lt；+/-&gt；)小鼠发展为动脉粥样硬化的确切机制。(1)计算动脉狭窄程度，分析血管内皮细胞活化、巨噬细胞泡沫化、清道夫受体表达、血管内膜β2-糖蛋白I(β2GPI)I的渗入、黏附分子和细胞因子的产生。(2)检测血清和/或脾细胞培养上清液中的β和Th2依赖细胞因子作为免疫标志物；(3)用流式细胞仪检测脾细胞表面标志。在对幽门螺杆菌阳性高血压患者的临床研究中，我们从病理生化、免疫学和临床免疫学的角度分析了幽门螺杆菌感染，尤其是幽门螺杆菌感染和抗HP-HSP60的体液免疫是否参与了动脉粥样硬化的发生。结果：幽门螺杆菌口腔感染可诱导抗HP-HSP60的Thl免疫应答，并导致动脉粥样硬化的发生。此外，我们最近观察到的与动脉粥样硬化发展相关的氧化低密度脂蛋白/低密度脂蛋白2GPI复合体与Hp-HSP60联合免疫显著降低了细胞免疫介导的动脉粥样硬化。由此可见，慢性感染的免疫应答加速了动脉粥样硬化的形成，疫苗接种阻止了动脉粥样硬化的发展，得到了伦理学的认可，为临床研究奠定了条件。我们观察到心血管跳水的发生与抗HP-HSP60抗体的出现显著相关，并在人类研究中成功克隆了HP-HSP60特异性T细胞。

In the present study, we studied precise mechanisms on the Helicobacter pylori (H pylori Infection)- infection develops atherosclerosis in atherosclerosis-prone model (apoe^<-/-> ldlr^<+/->) mice. Actually, (1) we calculated stricture grade of stethartery and analyzed activation of endothelial cells, foam cell formation of macrophages, expression of scavenger receptors, infiltration of β2-glycoprorein (β2GPI) I into the intima, production of adhesion molecules and cytokines. (2) As well as general blood parameters of lipid metabolism, oxidized LDL/β2GPI complexes and anti-Hp-HSP60 antibodies, Thl and Th2 dependent cytokines as immunologic markers in plasma and/or in supernatant of culture with splenocytes were also assayed (3) Further, surface markers of cultured splenocytes were detected by flow-cytometry. In clinical study with H pylori-positive hypertensive patients, we pathobiochemically, immunologically, and clinical immunologically analyzed whether infection, especially with H pylori and humeral immunity against Hp-HSP60 were involved in development of atherosclerosis. In results: the oral infection with H. pylori induced Thl immune response against Hp-HSP60 and resulted in developing atherosclerosis. Further, the cellular immunity-mediated atherosclerosis was significantly reduced by immunization with Hp-HSP60 together with adjuvant Plasma levels of novel marker of atherosclerosis, i.e., oxidized LDL/β2GPI complexes, which we have recently observed were associated with the development of atherosclerosis. Thus, it was shown a possibility that immune response to chronic infection accelerates atherosclerosis and vaccination prevents the development We got the ethical approval and establish the condition for the clinical study. We observed significant association between the development of cardiovascular dive and appearance of anti-Hp-HSP60 antibodies and successfully cloned a T cell specific to Hp-HSP60 in the human study.