Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education (M.G., P.M., W.H., Y.W., G.L., X.X.), Peking University, Beijing, China.
The School of Health Humanities (Z.L.), Peking University, Beijing, China.
Arterioscler Thromb Vasc Biol. 2020 Dec;40(12):2829-2836. doi: 10.1161/ATVBAHA.120.315265. Epub 2020 Oct 1.
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 (<8 months) and aged (>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 ≈40×10 μm in males and 18×10 μm 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 μmol/L in males and 30 μmol/L in females, which are significantly associated with the atherosclerotic lesions.
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.
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 是促动脉粥样硬化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，仓鼠中的 LCAT 缺乏（LCAT）会加速高脂肪饮食下的动脉粥样硬化发展。然而，与高胆固醇血症和高三酰甘油血症不同，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，我们试图在标准实验室饮食的 LCAT 仓鼠中研究动脉粥样硬化，并探讨潜在的潜在机制。
使用年轻（<8 个月）和老年（>16 个月）雄性和雌性野生型和 LCAT 仓鼠进行标准实验室饮食。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的血浆 HDL 完全丧失，并且甘油三酯增加了 2-8 倍。在老年 LCAT 仓鼠中，雄性主动脉根部的病变面积约为 40×10 μm，雌性约为 18×10 μm，分别与雄性（1.2%）和（1.5%）雌性组中观察到的正面斑块一致。血浆丙二醛测量结果表明，丙二醛浓度显着升高至雄性 54.4 μmol/L 和雌性 30 μmol/L，这与动脉粥样硬化病变明显相关。
我们的研究表明，在年龄较大的雄性和雌性 LCAT 仓鼠中，即使在血浆总胆固醇水平正常的情况下，也会自发发展出动脉粥样硬化病变，并且具有较高的血浆氧化脂质水平，进一步证实了 LCAT 的抗动脉粥样硬化作用。
