Associations of ApoAI and ApoB-containing lipoproteins with AngII-induced abdominal aortic aneurysms in mice.
Associations of ApoAI and ApoB-containing lipoproteins with AngII-induced abdominal aortic aneurysms in mice.
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DOI：
10.1161/atvbaha.115.305482
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Daugherty A
中科院分区：
文献类型：
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作者：
Liu J;Lu H;Howatt DA;Balakrishnan A;Moorleghen JJ;Sorci-Thomas M;Cassis LA;Daugherty A
血脂异常与人类和血管紧张素（Ang）II输注小鼠的腹主动脉瘤（AAA）有关。本研究使用多种小鼠品系，通过饮食和药理学操作，确定了主要脂蛋白类别对AngII诱导的AAA的影响。西方饮食对C57 BL/6 J小鼠的血浆胆固醇浓度和AngII诱导的AAAs的低发生率有轻微影响。低发病率的AAAs在这个菌株中并不归因于保护HDL，因为载脂蛋白（apo）AI缺乏没有增加血管紧张素II诱导的AAAs。ApoAI缺失也未能改变高胆固醇血症小鼠中AAA的发生。低密度脂蛋白（LDL）受体−/−小鼠喂食正常饮食，血管紧张素II诱导AAAs的发生率较低。西方饮食喂养的这种菌株引起了显着的高胆固醇血症，由于增加载脂蛋白B与随之而来的动脉粥样硬化的增加，在两种性别，但AAAs只在雄性小鼠。喂食正常饮食的ApoE−/−小鼠中度高胆固醇血症，而喂食西方饮食的该品系由于含apoB的脂蛋白浓度增加而严重高胆固醇血症。后者增加了动脉粥样硬化，但没有改变该菌株中AAAs的高发病率。为了确定含apoB的脂蛋白的减少是否影响AngII诱导的AAA，给予给予apoE−/−小鼠依折麦布，使其血浆胆固醇浓度部分降低。这减少了动脉粥样硬化，但不是AAA。在喂食正常饮食的apoE−/−小鼠中，该依折麦布剂量显著降低了血浆含apoB脂蛋白浓度，并降低了AngII诱导的AAA。含ApoB的脂蛋白有助于增强AngII诱导的雄性小鼠AAA。然而，与动脉粥样硬化不同，AAA的发生与血浆含apoB脂蛋白浓度的增加无关。
Dyslipidemia is implicated in abdominal aortic aneurysms (AAAs) in humans and angiotensin (Ang)II-infused mice. This study determined effects of major lipoprotein classes on AngII-induced AAAs using multiple mouse strains with dietary and pharmacological manipulations. Western diet had minor effects on plasma cholesterol concentrations and the low incidence of AngII-induced AAAs in C57BL/6J mice. Low incidence of AAAs in this strain was not attributed to protection from HDL, since apolipoprotein (apo)AI deficiency did not increase AngII-induced AAAs. ApoAI deletion also failed to alter AAA occurrence in hypercholesterolemic mice. Low density lipoprotein (LDL) receptor−/− mice fed normal diet had low incidence of AngII-induced AAAs. Western diet feeding of this strain provoked pronounced hypercholesterolemia due to increased apoB-containing lipoproteins with attendant increases of atherosclerosis in both genders, but AAAs only in male mice. ApoE−/− mice fed normal diet were modestly hypercholesterolemic, whereas this strain fed Western diet was severely hypercholesterolemic due to increased apoB-containing lipoprotein concentrations. The latter augmented atherosclerosis, but did not change the high incidence of AAAs in this strain. To determine whether reductions in apoB-containing lipoproteins influenced AngII-induced AAAs, ezetimibe was administered at a dose that partially reduced plasma cholesterol concentrations to apoE−/− mice fed Western diet. This decreased atherosclerosis, but not AAAs. This ezetimibe dose in apoE−/− mice fed normal diet significantly decreased plasma apoB-containing lipoprotein concentrations and reduced AngII-induced AAAs. ApoB-containing lipoproteins contribute to augmentation of AngII-induced AAA in male mice. However, unlike atherosclerosis, AAA occurrence was not correlated with increases in plasma apoB-containing lipoprotein concentrations.