Sebkhi A, Weinberg P D
School of Animal and Microbial Sciences, University of Reading, UK.
Arterioscler Thromb Vasc Biol. 1996 Feb;16(2):317-27. doi: 10.1161/01.atv.16.2.317.
Lipid deposition occurs more frequently downstream than upstream of branches in immature human aorta but the opposite pattern is seen in mature vessels. These distributions may reflect variation in the uptake of plasma macromolecules by the aortic wall. We have recently shown that the quasi-steady state uptake of albumin is greater downstream than upstream of branches in immature rabbit aortas and that the opposite pattern occurs in mature animals. Additionally, there is a sharp drop in the mean uptake shortly after weaning. In the present study, the mechanisms underlying these phenomena were investigated by examining the short-term uptake of albumin and its distribution across the wall. Albumin was labeled with a fluorescent dye and introduced into the circulation of conscious New Zealand White rabbits. Thoracic aortas were fixed in situ 10 minutes later and were sectioned through the center of intercostal ostia. Fluorescence from sections was measured by using digital imaging fluorescence microscopy and was converted to tracer concentrations after appropriate autofluorescence levels had been subtracted. In animals aged 45 days, more tracer was detected in the wall downstream than upstream of branches; the difference between regions was > 100% of the mean value. This percentage halved and the mean uptake decreased almost threefold by 75 days. In mature animals, the mean value remained at the 75-day level but the converse distribution was seen; 22% more tracer was detected upstream than downstream. These trends were insensitive to the depth of the intimal-medial layer examined. In each region, the maximum tracer concentration occurred close to the luminal surface but not always within the first 2.9-microns-thick layer of the wall. Maxima were similar in magnitude to those observed at quasi-steady state, but the fall with increasing distance into the wall was much sharper. In many cases concentrations remained constant over most of the media, and rises toward the adventitial boundary were rarely seen. Uptake after 10 minutes predominantly reflects the rate at which tracer enters the wall. The concentration profiles were consistent with most of the tracer having entered from the luminal surface and with the involvement of convective transport. The trends observed with age closely paralleled those occurring at quasi-steady state. Consequently, the latter are also likely to be determined by changes in the resistance of the wall to macromolecule influx.
在未成熟的人类主动脉中，脂质沉积在分支下游比上游更频繁地发生，但在成熟血管中则呈现相反的模式。这些分布可能反映了主动脉壁对血浆大分子摄取的差异。我们最近发现，未成熟兔主动脉中白蛋白的准稳态摄取在分支下游比上游更大，而在成熟动物中则出现相反的模式。此外，断奶后不久平均摄取量会急剧下降。在本研究中，通过检查白蛋白的短期摄取及其在整个管壁中的分布，对这些现象背后的机制进行了研究。用荧光染料标记白蛋白，并将其引入清醒的新西兰白兔的循环系统中。10分钟后将胸主动脉原位固定，并在肋间孔中心处进行切片。使用数字成像荧光显微镜测量切片的荧光，并在减去适当的自发荧光水平后将其转换为示踪剂浓度。在45天大的动物中，在分支下游的管壁中检测到的示踪剂比上游更多；区域之间的差异大于平均值的100%。到75天时，这个百分比减半，平均摄取量下降了近三倍。在成熟动物中，平均值保持在75天的水平，但观察到相反的分布；上游检测到的示踪剂比下游多22%。这些趋势对所检查的内膜-中膜层深度不敏感。在每个区域，最大示踪剂浓度出现在靠近管腔表面的位置，但并不总是在管壁的最初2.9微米厚的层内。最大值在大小上与在准稳态下观察到的相似，但随着进入管壁距离的增加，下降幅度要大得多。在许多情况下，在大部分中膜中浓度保持恒定，很少看到朝着外膜边界升高的情况。10分钟后的摄取主要反映了示踪剂进入管壁的速率。浓度分布与大多数示踪剂从管腔表面进入以及对流运输的参与相一致。随着年龄观察到的趋势与在准稳态下发生的趋势密切平行。因此，后者也可能由管壁对大分子流入的阻力变化所决定。
