| Co-Investigator(Kenkyū-buntansha) |
OGUMA keiji Okayama University, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Professor (00002262)
AYADA Kiyoshi Okayama University, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Assistant Professor (00379835)
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| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
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.
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