Characterization of Atherosclerosis Formation in a Murine Model of Type IIa Human Familial Hypercholesterolemia.
Characterization of Atherosclerosis Formation in a Murine Model of Type IIa Human Familial Hypercholesterolemia.
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DOI：
10.1155/2018/1878964
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发表时间：
2018
影响因子：
--
通讯作者：
Castellino FJ
中科院分区：
文献类型：
--
作者：
Miyajima C;Iwaki T;Umemura K;Ploplis VA;Castellino FJ
低密度脂蛋白胆固醇（LDL-C-）驱动的动脉粥样硬化小鼠遗传模型，基于低密度脂蛋白受体（Ldlr - / -）和载脂蛋白b -酶体复合物（Apobec1 - / -）的完全缺乏，该复合物将载脂蛋白b -100转化为载脂蛋白b -48，已经被广泛表征。这些基因缺陷使得高水平的载脂蛋白-100存在且无法有效清除，从而导致正常饮食小鼠的LDL-C水平非常高。在人类家族性高胆固醇血症中观察到的动脉粥样硬化斑块的许多关键特征在这些小鼠中被发现，因为它们被允许衰老到72周。一般特征包括血浆中存在高水平的LDL-C和巨噬细胞相关的主动脉树脂肪条纹形成，随着年龄的增长逐渐恶化。更具体地说，在主动脉窦中发现的斑块含有一个脂质核心，其中含有相对大量的巨噬细胞和一个平滑肌细胞α-肌动蛋白和胶原蛋白，随着年龄的增长而变薄。斑块进展的这些关键特征表明，Ldlr - / - /Apobec1 - / -小鼠系是ldl - c驱动的动脉粥样硬化的优越模型。
A murine genetic model of LDL-cholesterol- (LDL-C-) driven atherosclerosis, based on complete deficiencies of both the LDL-receptor (Ldlr−/−) and key catalytic component of an apolipoprotein B-edisome complex (Apobec1−/−), which converts apoB-100 to apoB-48, has been extensively characterized. These gene deficiencies allow high levels of apoB-100 to be present and inefficiently cleared, thus leading to very high levels of LDL-C in mice on a normal diet. Many key features of atherosclerotic plaques observed in human familial hypercholesterolemia are found in these mice as they are allowed to age through 72 weeks. The general characteristics include the presence of high levels of LDL-C in plasma and macrophage-related fatty streak formation in the aortic tree, which progressively worsens with age. More specifically, plaque found in the aortic sinuses contains a lipid core with relatively high numbers of macrophages and a smooth muscle cell α-actin- and collagen-containing cap, which thins with age. These critical features of plaque progression suggest that the Ldlr−/−/Apobec1−/− mouse line presents a superior model of LDL-C-driven atherosclerosis.
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动脉粥样硬化期间炎症的性别差异。
DOI：
10.4137/cmc.s17068
发表时间：
2014
期刊：
Clinical Medicine Insights. Cardiology
影响因子：
--
作者：
Fairweather D
通讯作者：
Fairweather D
影响因子：
15.9
作者：
ISHIBASHI, S;BROWN, MS;HERZ, J
通讯作者：
HERZ, J
影响因子：
2.4
作者：
Schmermund, Axel;Moehlenkamp, Stefan;Erbel, Raimund
通讯作者：
Erbel, Raimund
影响因子：
20.1
作者：
Kohno, M;Yokokawa, K;Yoshikawa, J
通讯作者：
Yoshikawa, J
影响因子：
120.7
作者：
CASTELLI, WP;GARRISON, RJ;KANNEL, WB
通讯作者：
KANNEL, WB