Masuda J, Ross R
Department of Pathology, University of Washington, Seattle 98195.
Arteriosclerosis. 1990 Mar-Apr;10(2):164-77. doi: 10.1161/01.atv.10.2.164.
Although a large body of data is available concerning atherogenesis in animals maintained at high levels of hypercholesterolemia, little data are available for animals maintained at lower levels of hypercholesterolemia for longer periods of time, closer to those observed in humans. The chronologic sequence of cellular events and interactions that occur during the formation of the lesions of atherosclerosis was investigated during relatively low level hypercholesterolemia (200 to 400 mg/dl) in a series of nonhuman primates (Macaca nemestrina). The arterial tree of each animal was examined by light microscopy and scanning and transmission electron microscopy. Immunohistochemical staining with monoclonal antibodies specific for smooth muscle cells, monocyte-macrophages, and T-lymphocytes was performed to analyze the cellular composition of the lesions. After 6 months of low level hypercholesterolemia, the surface of the aorta contained large numbers of adherent leukocytes, many of which were in the process of entering the artery. This resulted in irregularly shaped nodular elevations, or fatty streaks, preferentially located at branch sites and bifurcations. The fatty streaks consisted of intimal accumulations of numerous lipid-laden macrophages together with relatively small numbers of T-lymphocytes. With lesion progression, the thickness of the fatty streaks increased, and their surfaces became irregular and frequently showed disruptions of covering endothelial cells resulting in exposure of subendothelial macrophages. Platelet microthrombi were observed over some of the exposed macrophages at some branches or bifurcations in every animal studied. These observations made during the early phases of atherosclerosis lesion formation are virtually identical to those described in our previous reports in high level hypercholesterolemic nonhuman primates (600 to 1000 mg/dl) with the exception that the changes occurred more slowly in the lower levels of hypercholesterolemia.
尽管有大量关于维持高胆固醇血症水平的动物动脉粥样硬化形成的数据，但关于维持较低水平高胆固醇血症较长时间（更接近人类观察到的水平）的动物的数据却很少。在一系列食蟹猴（Macaca nemestrina）中，研究了在相对低水平高胆固醇血症（200至400mg/dl）期间动脉粥样硬化病变形成过程中细胞事件和相互作用的时间顺序。通过光学显微镜、扫描电子显微镜和透射电子显微镜检查每只动物的动脉树。用针对平滑肌细胞、单核细胞-巨噬细胞和T淋巴细胞的单克隆抗体进行免疫组织化学染色，以分析病变的细胞组成。在低水平高胆固醇血症6个月后，主动脉表面有大量黏附的白细胞，其中许多正在进入动脉。这导致了形状不规则的结节状隆起，即脂肪条纹，优先位于分支部位和分叉处。脂肪条纹由大量富含脂质的巨噬细胞以及相对少量的T淋巴细胞在内膜的积聚组成。随着病变进展，脂肪条纹厚度增加，其表面变得不规则，并经常显示覆盖的内皮细胞破裂，导致内皮下巨噬细胞暴露。在每只研究动物的一些分支或分叉处，在一些暴露的巨噬细胞上观察到血小板微血栓。在动脉粥样硬化病变形成早期阶段的这些观察结果与我们之前关于高水平高胆固醇血症食蟹猴（600至1000mg/dl）的报告中描述的结果几乎相同，只是在较低水平高胆固醇血症中变化发生得更慢。
