作者机构：
[Hao, Xinrui; Ou, Xiang; Tang, Yaling; Hu, Yanwei; Li, Xiaoxu; Tang, Chaoke; Cao, Dongli; Dai, Xiaoyan] Univ S China, Key Lab Atherosclerol Human Prov, Cardiovasc Res Inst, Hengyang 421001, Peoples R China.
通讯机构：
[Tang, Chaoke] U;Univ S China, Key Lab Atherosclerol Human Prov, Cardiovasc Res Inst, Hengyang 421001, Peoples R China.
关键词：
semicarbazide-sensitive amine oxidase;nuclear receptor;liver X receptor;T0901317;atherosclerosis
摘要：
Semicarbazide-sensitive amine oxidase (SSAO) catalyzes oxidative deamination of primary aromatic and aliphatic amines. Increased SSAO activity has been found in atherosclerosis and diabetes mellitus. We hypothesize that the anti-atherogenic effect of liver X receptors (LXRs) might be related to the inhibition of SSAO gene expression and its activity. In this study, we investigated the effect of LXRagonist T0901317 on SSAO gene expression and its activity in apolipoprotein E knockout (apoE−/−) mice. Male apoE−/− mice (8 weeks old) were randomly divided into four groups: basal control group; vehicle group; prevention group; and treatment group. SSAO gene expression was analyzed by real-time quantitative polymerase chain reaction and its activity was determined. The activity of superoxide dismutase and content of malondialdehyde in the aorta and liver were also determined. In T0901317-treated mice, SSAO gene expression was significantly decreased in the aorta, liver, small intestine, and brain. SSAO activities in serum and in these tissues were also inhibited. The amount of superoxide dismutase in the aorta and liver of the prevention group and treatment group was significantly higher compared with the vehicle group (P < 0.05). Malondialdehyde in the tissues of these two groups was significantly lower compared with the vehicle group (P < 0.05). Our results showed that T0901317 inhibits SSAO gene expression and its activity in atherogenic apoE−/− mice. The atheroprotective effect of LXR agonist T0901317 is related to the inhibition of SSAO gene expression and its activity.
作者机构：
[Hu YanWei; Ou Xiang; Dai XiaoYan; Tang ChaoKe; Hao XinRui; Tang YaLing; Cao DongLi; Li XiaoXu] Univ S China, Key Lab Atherosclerol Hunan Province, Inst Cardiovasc Res, Hengyang 421001, Peoples R China.;[Ou Xiang] Shaoguan Univ, Dept Physiol, Coll Med, Shaoguan 512026, Peoples R China.;[Long ZhiFeng] Univ S China, Dept Histol & Embryol, Hengyang 421001, Peoples R China.
通讯机构：
[Tang ChaoKe] U;Univ S China, Key Lab Atherosclerol Hunan Province, Inst Cardiovasc Res, Hengyang 421001, Peoples R China.
关键词：
Niemann-Pick C1 protein;liver X receptor agonist;atherosclerosis;plaque
摘要：
In this study, we studied the effect of liver X receptor (LXR) agonist T0901317 on Niemann-Pick C1 protein (NPC1) expression in apoE-/- mice. Male apoE-/- mice were randomized into 4 groups, baseline group (n=10), control group (n = 14), treatment group (n = 14) and prevention group (n = 14). All of the mice were fed with a high-fat/high-cholesterol (HFHC) diet containing 15% fat and 0.25% cholesterol. The baseline group treated with vehicle was sacrificed after 8 weeks of the diet. The control group and the prevention group were treated with either vehicle or T0901317 daily by oral gavage for 14 weeks. The treatment group was treated with vehicle for 8 weeks, and then was treated with the agonist T0901317 for additional 6 weeks. Gene and protein expression was analyzed by real-time quantitative PCR, immunohistochemistry and Western blotting, respectively. Plasma lipid concentrations were measured by commercially enzymatic methods. We used RNA interference technology to silence NPC1 gene expression in THP-1 macrophage-derived foam cells and then detected the effect of LXR agonist T0901317 on cholesterol efflux. Plasma triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and apoA-I concentrations were markedly increased in T0901317-treated groups. T0901317 treatment reduced the aortic atherosclerotic lesion area by 64.2% in the prevention group and 58.3% in the treatment group. LXR agonist treatment increased NPC1 mRNA expression and protein levels in the small intestine, liver and aorta of apoE-/- mice. Compared with the normal cells, cholesterol efflux of siRNA THP-1 macrophage-derived foam cells was significantly decreased, whereas cholesterol efflux of LXR agonist T0901317-treated THP-1 macrophage-derived foam cells was significantly increased. Our results suggest that LXR agonist T0901317 inhibits atherosclerosis development in apoE-/- mice, which is related to up-regulating NPC1 expression.
摘要：
目的 研究高密度脂蛋白(high density lipoprotein,HDL)及其亚类对ECV304细胞产生组织因子的调控作用.方法 实验分对照组(未加任何刺激因素)、刺激因素组(分别加组胺、凝血酶和氧化型高密度脂蛋白)和刺激因素加高密度脂蛋白及其亚类组.用TRIZOL法抽提RNA,普通PCR、实时定量PCR检测组织因子表达情况.结果 未加任何刺激因素的ECV304细胞不表达组织因子.刺激因素组:(1)组胺、凝血酶和氧化型高密度脂蛋白(oxidized high density lipoprotein)均能刺激ECV304细胞产生组织因子(P＜0.05).(2)刺激因素加高密度脂蛋白及其亚类组分别跟加相同刺激因素组相比,均能使组织因子的表达下降.其中HDL对组胺诱导的组织因子表达与对照组相比降低近50%(P＜0.05).HDL2对组胺诱导的组织因子表达下调12%(P＜0.05).HDL、HDL2和HDL3对凝血酶诱导的组织因子的表达分别下调6%、16%和14%(P＜0.05).结论 凝血酶、组胺和氧化型高密度脂蛋白均能刺激ECV304细胞产生组织因子,高密度脂蛋白及其亚类可抑制这些因素刺激的组织因子表达上调.
