Spontaneous Atherosclerosis in Aged LCAT-Deficient Hamsters With Enhanced Oxidative Stress-Brief Report
Spontaneous Atherosclerosis in Aged LCAT-Deficient Hamsters With Enhanced Oxidative Stress-Brief Report
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DOI：
10.1161/atvbaha.120.315265
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发表时间：
2020-12-01
影响因子：
8.7
通讯作者：
Xian, Xunde
中科院分区：
文献类型：
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作者：
Guo, Mengmeng;Liu, Zongyu;Xian, Xunde
目的：LCAT（卵磷脂胆固醇酰基转移酶）缺乏导致严重的低HDL（高密度脂蛋白）。尽管在小鼠研究中LCAT是促进还是抗动脉粥样硬化存在争议，但我们之前的研究清楚地表明，仓鼠高脂肪饮食中LCAT缺乏（LCAT(-/-)）会加速动脉粥样硬化的发展。然而，与高胆固醇血症和高甘油三酯血症不同，LCAT缺乏是否会导致自发性动脉粥样硬化尚未在动物模型中进行研究。因此，我们试图研究LCAT（-/-）仓鼠在标准实验室饮食中的动脉粥样硬化，并探索潜在的潜在机制。方法和结果：采用标准实验室饮食的幼年（16个月）雄性和雌性野生型和LCAT（-/-）仓鼠。与年龄和性别匹配的野生型仓鼠相比，LCAT（-/-）仓鼠在不同年龄阶段显示血浆HDL完全丧失，甘油三酯增加2- 8倍。老龄LCAT（-/-）仓鼠主动脉根部病变面积雄性约为40 × 10(4) μ m(3)，雌性约为18 × 10(4) μ m(3)，与雄性组（1.2%）和雌性组（1.5%）的表面斑块一致。血浆丙二醛测定结果显示，男性丙二醛浓度显著升高至54.4 μ mol/L，女性丙二醛浓度为30 μ mol/L，与动脉粥样硬化病变显著相关。结论：我们的研究证实了老年LCAT（-/-）雄性和雌性仓鼠自发性动脉粥样硬化病变的发展，其血浆氧化脂水平较高，不依赖于血浆总胆固醇水平，进一步证实了LCAT的抗动脉粥样硬化作用。
Objective:LCAT (lecithin cholesterol acyltransferase) deficiency results in severe low HDL (high-density lipoprotein). Although whether LCAT is pro- or antiatherosclerosis was in debate in mouse studies, our previous study clearly shows that LCAT deficiency (LCAT(-/-)) in hamster accelerates atherosclerotic development on high-fat diet. However, unlike in hypercholesterolemia and hypertriglyceridemia, whether LCAT deficiency could lead to spontaneous atherosclerosis has not been studied yet in animal models. We, therefore, sought to investigate the atherosclerosis in LCAT(-/-) hamsters on standard laboratory diet and explore the potential underlying mechanisms.Approach and Results:Young (16 months) male and female wild-type and LCAT(-/-) hamsters on standard laboratory diet were used. Compared with age- and sex-matched wild-type hamsters, LCAT(-/-) hamsters showed a complete loss of plasma HDL and an increase in triglyceride by 2- to 8-fold at different stages of age. In aged LCAT(-/-) hamsters, the lesion areas at the aortic roots were approximate to 40x10(4) mu m(3) in males and 18x10(4) mu m(3) in females, respectively, which were consistent with the en face plaques observed in male (1.2%) and (1.5%) female groups, respectively. The results of plasma malondialdehyde measurement showed that malondialdehyde concentrations were markedly elevated to 54.4 mu mol/L in males and 30 mu mol/L in females, which are significantly associated with the atherosclerotic lesions.Conclusions:Our study demonstrates the development of spontaneous atherosclerotic lesions in aged male and female LCAT(-/-) hamsters with higher plasma oxidative lipid levels independent of plasma total cholesterol levels, further confirming the antiatherosclerotic role of LCAT.