ATHEROGENESIS DURING LOW-LEVEL HYPERCHOLESTEROLEMIA IN THE NONHUMAN PRIMATE .1. FATTY STREAK FORMATION
ATHEROGENESIS DURING LOW-LEVEL HYPERCHOLESTEROLEMIA IN THE NONHUMAN PRIMATE .1. FATTY STREAK FORMATION
复制标题
DOI：
10.1161/01.atv.10.2.164
复制
发表时间：
1990-03-01
期刊：
影响因子：
--
通讯作者：
ROSS, R
中科院分区：
文献类型：
--
作者：
MASUDA, J;ROSS, R
虽然大量的数据是关于维持在高水平的高胆固醇血症的动物中的动脉粥样硬化形成的，但几乎没有数据可用于维持在较低水平的高胆固醇血症较长时间的动物，更接近于在人类中观察到的那些。在一系列非人灵长类动物（Macaca nemestrina）相对低水平的高胆固醇血症（200至400 mg/dl）期间，研究了动脉粥样硬化病变形成过程中发生的细胞事件和相互作用的时序。通过光学显微镜、扫描和透射电子显微镜检查每只动物的动脉树。用平滑肌细胞、单核-巨噬细胞和T淋巴细胞特异性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。低水平高胆固醇血症6个月后，主动脉表面含有大量粘附的白细胞，其中许多正在进入动脉的过程中。这导致不规则形状的结节隆起或脂肪条纹，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淋巴细胞的内膜积聚组成。随着病变的进展，脂肪条纹的厚度增加，它们的表面变得不规则，并经常显示覆盖内皮细胞的破坏，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的早期阶段进行的这些观察结果与我们以前在高水平高胆固醇血症非人灵长类动物（600至1000 mg/dl）中的报告中描述的结果几乎相同，只是在低水平高胆固醇血症中变化发生得更慢。
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 disurptions 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.