StAR overexpression decreases serum and tissue lipids in apolipoprotein E-deficient mice.
StAR overexpression decreases serum and tissue lipids in apolipoprotein E-deficient mice.
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StAR 过表达降低载脂蛋白 E 缺陷小鼠的血清和组织脂质
DOI：
10.1007/s11745-009-3299-1
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发表时间：
2009-06
期刊：
影响因子：
1.9
通讯作者：
Yin, Lianhua
中科院分区：
文献类型：
--
作者：
Ning, Yanxia;Xu, Leyuan;Ren, Shunlin;Pandak, William M.;Chen, Sifeng;Yin, Lianhua
由线粒体甾醇27-羟化酶（CYP27A1）启动的胆固醇代谢是一种普遍存在的途径，能够合成参与脂质稳态的多种关键调节氧化甾醇。先前我们已经表明，其在肝细胞内的活性调节是由线粒体胆固醇输送率高度控制的。在本研究中，我们假设线粒体胆固醇传递蛋白，类固醇急性调节蛋白（StAR）的表达增加，能够降低肝脏，主动脉壁以及血清中的脂质积累，在一个有充分记录的动物模型中，载脂蛋白e缺陷（apoE−/−）小鼠。用重组巨细胞病毒(CMV)-StAR腺病毒感染3月龄时血清、肝脏和内皮细胞胆固醇和甘油三酯水平升高的ApoE−/−小鼠，以增加StAR蛋白的表达。感染后6天，血清总胆固醇和甘油三酯分别下降19%和30% (P< 0.01)，与对照组（无病毒或对照组）相比，增加StAR表达小鼠血清高密度脂蛋白胆固醇代偿性增加40% （P< 0.01）。肝脏的组织学和生化分析表明，不仅胆固醇显著降低（↓25%；P< 0.01），而且甘油三酯含量显著降低（↓56%；P< 0.01）。动脉整体Sudan IV染色显示中性脂质染色减少bbb80 % （P< 0.01）。本研究首次证明了cyp27a1启动通路在治疗血脂异常中的可能治疗作用。
Cholesterol metabolism as initiated by mitochondrial sterol 27-hydroxylase (CYP27A1) is a ubiquitous pathway capable of synthesizing multiple key regulatory oxysterols involved in lipid homeostasis. Previously we have shown that the regulation of its activities within hepatocytes is highly controlled by the rate of mitochondrial cholesterol delivery. In the present study, we hypothesized that increasing expression of the mitochondrial cholesterol delivery protein, steroidogenic acute regulatory protein (StAR), is able to lower lipid accumulation in liver, aortic wall, as well as in serum in a well-documented animal model, apolipoprotein E-deficient (apoE−/−) mice. ApoE−/−mice, characterized by increased serum, liver, and endothelial cholesterol and triglyceride levels by 3 months of age, were infected with recombinant cytomegalovirus (CMV)-StAR adenovirus to increase StAR protein expression. Six days following infection, serum total cholesterol and triglycerides had decreased 19 and 30% (P< 0.01), respectively, with a compensatory 40% (P< 0.01) increase in serum HDL-cholesterol in increased StAR expressing mice as compared to controls (no or control virus). Histologic and biochemical analysis of the liver demonstrated not only a dramatic decrease in cholesterol (↓25%;P< 0.01), but an even more marked decrease in triglyceride (↓56%;P< 0.01) content. En bloc Sudan IV staining of the aorta revealed a >80% (P< 0.01) decrease in neutral lipid staining. This study demonstrates for the first time a possible therapeutic role of the CYP27A1-initiated pathway in the treatment of dyslipidemias.
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影响因子：
15.9
作者：
Jefcoate, C
通讯作者：
Jefcoate, C
影响因子：
15.9
作者：
OFTEBRO, H;BJORKHEM, I;PEDERSEN, JI
通讯作者：
PEDERSEN, JI
DOI：
10.1161/01.atv.14.1.133
发表时间：
1994-01-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
NAKASHIMA, Y;PLUMP, AS;ROSS, R
通讯作者：
ROSS, R
影响因子：
8.7
作者：
d'Uscio, LV;Baker, TA;Katusic, ZS
通讯作者：
Katusic, ZS
影响因子：
6.7
作者：
Ma, Y.;Ren, S.;Yin, L.
通讯作者：
Yin, L.