Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA.
Mol Neurodegener. 2009 Oct 24;4:42. doi: 10.1186/1750-1326-4-42.
Hypercholesterolemia causes atherosclerosis in medium to large sized arteries. Cholesterol is less known for affecting the microvasculature and has not been previously reported to induce microvascular pathology in the central nervous system (CNS).
Mice with a null mutation in the low-density lipoprotein receptor (LDLR) gene as well as C57BL/6J mice fed a high cholesterol diet developed a distinct microvascular pathology in the CNS that differs from cholesterol-induced atherosclerotic disease. Microvessel diameter was increased but microvascular density and length were not consistently affected. Degenerative changes and thickened vascular basement membranes were present ultrastructurally. The observed pathology shares features with the microvascular pathology of Alzheimer's disease (AD), including the presence of string-like vessels. Brain apolipoprotein E levels which have been previously found to be elevated in LDLR-/- mice were also increased in C57BL/6J mice fed a high cholesterol diet.
In addition to its effects as an inducer of atherosclerosis in medium to large sized arteries, hypercholesterolemia also induces a microvascular pathology in the CNS that shares features of the vascular pathology found in AD. These observations suggest that high cholesterol may induce microvascular disease in a range of CNS disorders including AD.
高胆固醇血症会导致大中动脉的动脉粥样硬化。胆固醇对微血管的影响鲜为人知，以前也没有报道过它会在中枢神经系统 (CNS) 引起微血管病变。
载脂蛋白 E 基因缺失的低密度脂蛋白受体 (LDLR) 基因敲除小鼠以及喂食高胆固醇饮食的 C57BL/6J 小鼠在中枢神经系统中出现了一种独特的微血管病变，与胆固醇诱导的动脉粥样硬化疾病不同。微血管直径增加，但微血管密度和长度没有一致受到影响。超微结构上存在退行性改变和血管基底膜增厚。观察到的病理学与阿尔茨海默病 (AD) 的微血管病理学具有共同特征，包括存在线状血管。先前发现 LDLR-/- 小鼠脑载脂蛋白 E 水平升高，喂食高胆固醇饮食的 C57BL/6J 小鼠的载脂蛋白 E 水平也升高。
除了作为大中动脉动脉粥样硬化的诱导剂外，高胆固醇血症还会在中枢神经系统中引起一种与 AD 中发现的血管病理学具有共同特征的微血管病理学。这些观察结果表明，高胆固醇可能会在包括 AD 在内的一系列中枢神经系统疾病中引起微血管疾病。
