Vascular remodeling in Nox1/NADPH oxidase deficient mice

NADPH氧化酶是一种产生超氧化物的酶，由多个亚基组成，包括跨膜催化亚基Nox。Nox 1是一种新发现的Nox亚型，与血管紧张素II诱导的高血压的发生有关。我们最近观察到，在注射脂多糖（LPS）的小鼠的主动脉中，Nox 1基因的表达上调。由于长期暴露于内毒素（如牙周病）是动脉粥样硬化的危险因素，我们使用基因修饰小鼠检测Nox 1/NADPH氧化酶活性增加是否与血管重塑的发展相关。处死维持高脂肪饮食4至24周的DKO小鼠，并对分离的睾丸进行油红O染色。血管紧张素II（500 ng/kg/min）处理组与对照组相比，动脉粥样硬化区面积无显著性差异。因此，Nox 1/NADPH氧化酶的缺失并不影响小鼠动脉粥样硬化的发展。我们目前正在研究Nox 1/NADPH氧化酶在内毒素诱导的致死性休克发病机制中的作用。

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.