Key Laboratory of Molecular Cardiovascular Sciences, Institute of Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, China.
School of Medicine, Shihezi University, Shihezi City, Xinjiang Uygur Autonomous Region 832000, China.
Cells. 2019 Sep 4;8(9):1028. doi: 10.3390/cells8091028.
While high low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) levels are positively associated with cardiovascular events, it is still unclear whether familial hypercholesterolemia (FH) and Tangier's disease (TD), caused by mutations in LDLR and ABCA1, respectively, influence ischemic stroke (IS) in humans.
We sought to establish an easier, more effective, and time-saving method to induce IS, then studied the precise effects of different types of lipoproteins on IS.
A new technique termed contralateral middle cerebral artery occlusion (c-MCAO) was introduced to human-like hamster models to induce IS. Compared to traditional distal MCAO (d-MCAO) induced by electrocoagulation, c-MCAO resulted in a more severe IS with larger infarct sizes and more blood-brain barrier (BBB) disruption after 24 h. It was shown that c-MCAO markedly elicited an increase in brain infarct volume and BBB leakage in both homozygous LDLR (LDLR) and ABCA1 knockout (ABCA1) hamsters, but not in heterozygous LDLR knockout (LDLR) hamsters when compared to wild-type (WT) controls.
Using human-like genetically engineered hamsters, our findings demonstrated that both high LDL-C level caused by homozygous LDLR deficiency and severe low HDL-C level caused by deleting ABCA1 were risk factors of IS. As such, we believe the development of this novel IS hamster model is suitable for future ischemic/reperfusion studies.
虽然高低密度脂蛋白胆固醇（LDL-C）和低高密度脂蛋白胆固醇（HDL-C）水平与心血管事件呈正相关，但家族性高胆固醇血症（FH）和 Tangier 病（TD）分别由 LDLR 和 ABCA1 的突变引起，是否会影响人类缺血性中风（IS）仍不清楚。
我们试图建立一种更简单、更有效、更省时的诱导 IS 的方法，然后研究不同类型的脂蛋白对 IS 的精确影响。
一种新的技术，称为对侧大脑中动脉闭塞（c-MCAO），被引入到类人仓鼠模型中以诱导 IS。与传统的电凝诱导的远端大脑中动脉闭塞（d-MCAO）相比，c-MCAO 导致更严重的 IS，梗死面积更大，24 小时后血脑屏障（BBB）破坏更严重。结果表明，与野生型（WT）对照组相比，c-MCAO 明显引起纯合 LDLR（LDLR）和 ABCA1 敲除（ABCA1）仓鼠的脑梗死体积和 BBB 渗漏明显增加，但杂合 LDLR 敲除（LDLR）仓鼠则不然。
使用类人基因工程仓鼠，我们的研究结果表明，由 LDLR 纯合缺失引起的高 LDL-C 水平和由 ABCA1 缺失引起的严重低 HDL-C 水平都是 IS 的危险因素。因此，我们相信这种新型 IS 仓鼠模型的开发适合未来的缺血/再灌注研究。
