PDF(Pubmed)
Abstract：
UNASSIGNED: Apolipoprotein E (apoE) acts as a binding molecule for both the low-density lipoprotein receptor and the lipoprotein receptor-related protein and this function is essential for facilitating the hepatocyte uptake of lipoproteins containing apoB. The absence of apoE leads to increased atherogenicity in both humans and mice, although the precise molecular mechanisms remain incompletely understood.
UNASSIGNED: This study aimed to investigate the susceptibility of apoE knockout (KO) rabbits, in comparison with wild-type (WT) rabbits, to diet-induced hyperlipidemia and atherosclerosis.
UNASSIGNED: ApoE KO rabbits and WT rabbits were fed a diet containing 0.3% cholesterol for 16 weeks. Plasma lipid levels, lipoproteins, and apolipoproteins were analyzed. Atherosclerosis was evaluated at the endpoint of experiments. In addition, we evaluated the oxidizability of those lipoproteins containing apoB to investigate the possible mechanisms of atherosclerosis.
UNASSIGNED: Male apoE KO rabbits showed significantly elevated levels of total cholesterol and triglycerides compared to WT rabbits, while female apoE KO rabbits displayed similar high total cholesterol levels, albeit with significantly higher triglycerides levels than WT controls. Notably, both male (2.1-fold increase) and female (1.6-fold increase) apoE KO rabbits exhibited a significantly augmented aortic lesion area compared to WT controls. Pathological examination showed that the increased intimal lesions in apoE KO rabbits were featured by heightened infiltration of macrophages (2.7-fold increase) and smooth muscle cells (2.5-fold increase). Furthermore, coronary atherosclerotic lesions were also increased by 1.3-fold in apoE KO rabbits. Lipoprotein analysis revealed that apoB48-rich beta-very-low-density lipoproteins were notably abundant in apoE KO rabbits, suggesting that these remnant lipoproteins of intestinal origin serve as the primary atherogenic lipoproteins. Moreover, apoB48-rich remnant lipoproteins isolated from apoE KO rabbits exhibited heightened susceptibility to copper-induced oxidation.
UNASSIGNED: The findings indicate that apoB48-rich remnant lipoproteins, resulting from apoE deficiency, possess greater atherogenic potential than apoB100-rich remnant lipoproteins, regardless of plasma TC levels.
UNASSIGNED: This study aimed to investigate the susceptibility of apoE knockout (KO) rabbits, in comparison with wild-type (WT) rabbits, to diet-induced hyperlipidemia and atherosclerosis.
UNASSIGNED: ApoE KO rabbits and WT rabbits were fed a diet containing 0.3% cholesterol for 16 weeks. Plasma lipid levels, lipoproteins, and apolipoproteins were analyzed. Atherosclerosis was evaluated at the endpoint of experiments. In addition, we evaluated the oxidizability of those lipoproteins containing apoB to investigate the possible mechanisms of atherosclerosis.
UNASSIGNED: Male apoE KO rabbits showed significantly elevated levels of total cholesterol and triglycerides compared to WT rabbits, while female apoE KO rabbits displayed similar high total cholesterol levels, albeit with significantly higher triglycerides levels than WT controls. Notably, both male (2.1-fold increase) and female (1.6-fold increase) apoE KO rabbits exhibited a significantly augmented aortic lesion area compared to WT controls. Pathological examination showed that the increased intimal lesions in apoE KO rabbits were featured by heightened infiltration of macrophages (2.7-fold increase) and smooth muscle cells (2.5-fold increase). Furthermore, coronary atherosclerotic lesions were also increased by 1.3-fold in apoE KO rabbits. Lipoprotein analysis revealed that apoB48-rich beta-very-low-density lipoproteins were notably abundant in apoE KO rabbits, suggesting that these remnant lipoproteins of intestinal origin serve as the primary atherogenic lipoproteins. Moreover, apoB48-rich remnant lipoproteins isolated from apoE KO rabbits exhibited heightened susceptibility to copper-induced oxidation.
UNASSIGNED: The findings indicate that apoB48-rich remnant lipoproteins, resulting from apoE deficiency, possess greater atherogenic potential than apoB100-rich remnant lipoproteins, regardless of plasma TC levels.
摘要：
■载脂蛋白E（apoE）充当低密度脂蛋白受体和脂蛋白受体相关蛋白的结合分子，该功能对于促进肝细胞摄取含apoB的脂蛋白至关重要。apoE的缺失导致人和小鼠动脉粥样硬化的增加，尽管精确的分子机制仍未完全理解。
■本研究旨在研究apoE基因敲除（KO）兔的易感性，与野生型（WT）兔相比，饮食诱导的高脂血症和动脉粥样硬化。
■ApoEKO兔和WT兔饲喂含有0.3％胆固醇的饮食16周。血浆脂质水平，脂蛋白,和载脂蛋白进行了分析。在实验终点评估动脉粥样硬化。此外,我们评估了含有apoB的脂蛋白的氧化性，以研究动脉粥样硬化的可能机制。
■雄性apoEKO兔与WT兔相比，总胆固醇和甘油三酯水平显着升高，而雌性apoEKO兔表现出相似的高总胆固醇水平，尽管甘油三酯水平明显高于WT对照。值得注意的是,与WT对照组相比，雄性（增加2.1倍）和雌性（增加1.6倍）apoEKO兔的主动脉病变面积显着增加。病理检查表明，apoEKO兔的内膜病变增加，其特征是巨噬细胞浸润增加（增加2.7倍）和平滑肌细胞浸润增加（增加2.5倍）。此外，apoEKO兔的冠状动脉粥样硬化病变也增加了1.3倍。脂蛋白分析显示，富含apoB48的β-极低密度脂蛋白在apoEKO兔中尤其丰富，这表明这些肠道来源的残留脂蛋白是主要的动脉粥样硬化脂蛋白。此外，从apoEKO兔子中分离出的富含apoB48的残留脂蛋白对铜诱导的氧化具有更高的敏感性。
■研究结果表明，富含apoB48的残留脂蛋白，由于apoE缺乏，具有比富含apoB100的残留脂蛋白更大的动脉粥样硬化潜力，无论血浆TC水平。
■本研究旨在研究apoE基因敲除（KO）兔的易感性，与野生型（WT）兔相比，饮食诱导的高脂血症和动脉粥样硬化。
■ApoEKO兔和WT兔饲喂含有0.3％胆固醇的饮食16周。血浆脂质水平，脂蛋白,和载脂蛋白进行了分析。在实验终点评估动脉粥样硬化。此外,我们评估了含有apoB的脂蛋白的氧化性，以研究动脉粥样硬化的可能机制。
■雄性apoEKO兔与WT兔相比，总胆固醇和甘油三酯水平显着升高，而雌性apoEKO兔表现出相似的高总胆固醇水平，尽管甘油三酯水平明显高于WT对照。值得注意的是,与WT对照组相比，雄性（增加2.1倍）和雌性（增加1.6倍）apoEKO兔的主动脉病变面积显着增加。病理检查表明，apoEKO兔的内膜病变增加，其特征是巨噬细胞浸润增加（增加2.7倍）和平滑肌细胞浸润增加（增加2.5倍）。此外，apoEKO兔的冠状动脉粥样硬化病变也增加了1.3倍。脂蛋白分析显示，富含apoB48的β-极低密度脂蛋白在apoEKO兔中尤其丰富，这表明这些肠道来源的残留脂蛋白是主要的动脉粥样硬化脂蛋白。此外，从apoEKO兔子中分离出的富含apoB48的残留脂蛋白对铜诱导的氧化具有更高的敏感性。
■研究结果表明，富含apoB48的残留脂蛋白，由于apoE缺乏，具有比富含apoB100的残留脂蛋白更大的动脉粥样硬化潜力，无论血浆TC水平。
