Vascular remodeling in Nox1/NADPH oxidase deficient mice

Nox1/NADPH 氧化酶缺陷小鼠的血管重塑

• 批准号: 17590225
• 负责人: YABE Chihiro
• 金额: $ 2.3万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590225/
• 关键词: Genetically modified mice; Reactive oxygen species; Cardiovascular system; 遺伝子; 酵素; 循環器・高血圧

NADPH oxidase is a superoxide-generating enzyme composed of multiple subunits including a membrane-spanning catalytic subunit, Nox. A newly identified isoform of Nox, Nox1 has been implicated in the development of angiotensin II-induced hypertension. We recently observed that the expression of the Nox1 gene is upregulated in the aorta of mice injected with lipopolysaccharide (LPS). Since chronic exposure to endotoxin (such as in periodontal disease) is a risk factor of atherosclerosis, we examined whether increased activity of Nox1 /NADPH oxidase is associated with the development of vascular remodeling using genetically modified mice.Nox1-deficient mice (KO) were crossed with apoE-deficient mice to generate double knockout (DKO) mice. DKO mice maintained on high fat diet for 4 to 24 weeks were sacrificed, and isolated aortas were subjected to Oil red O staining. No difference was observed in the area of atherosclerotic region between DKO and KO treated with or without angiotensin II (500ng/kg/min). Accordingly, the absence of Nox1 /NADPH oxidase did not affect the development of atherosclerosis in mice.Following LPS injection, the expression of Nox1 mRNA was markedly elevated in many organs. We are currently investigating the role of Nox1 /NADPH oxidase in the pathogenesis of endotoxin-induced lethal shock.

NADPH氧化酶是一种由多个亚基组成的超氧化物生成酶，包括跨膜催化亚基Nox。Nox1是一种新发现的Nox异构体，与血管紧张素ii诱导的高血压的发展有关。我们最近观察到注射脂多糖（LPS）的小鼠主动脉中Nox1基因的表达上调。由于长期暴露于内毒素（如牙周病）是动脉粥样硬化的一个危险因素，我们使用转基因小鼠研究了Nox1 /NADPH氧化酶活性的增加是否与血管重构的发展有关。将nox1缺陷小鼠（KO）与apoe缺陷小鼠杂交，生成双敲除（DKO）小鼠。处死高脂饮食4 ~ 24周的DKO小鼠，取离体主动脉油红O染色。使用或不使用血管紧张素II （500ng/kg/min）治疗的DKO和KO的动脉粥样硬化区面积没有差异。因此，Nox1 /NADPH氧化酶的缺失不影响小鼠动脉粥样硬化的发展。注射LPS后，Nox1 mRNA在许多器官的表达明显升高。我们目前正在研究Nox1 /NADPH氧化酶在内毒素致死性休克发病机制中的作用。