Betz E, Fallier-Becker P, Wolburg-Buchholz K, Fotev Z
Institute of Physiology (I), Tübingen, Federal Republic of Germany.
J Cell Physiol. 1991 Jun;147(3):385-95. doi: 10.1002/jcp.1041470302.
During the development of atherosclerotic and fibromuscular proliferates/lesions, smooth muscle cells (SMC) in the media, particularly near the lumen, are activated to migrate into the intima, where they continue to proliferate to form an intimal thickening. It is to date unclear whether SMCs situated adjacent to the adventitia possess a lower capacity to proliferate because they are a special subpopulation of medial SMCs or because the adventitia excerts an inhibitory effect. We have, therefore, developed an in vitro system whereby we have attempted to clear up this uncertainty. The following observations were made from the in vitro experiments: Media-explants from rabbit aorta were laid on a polycarbonate filter with pores 5 microns in diameter. The SMCs migrated through the pores and formed a fibromuscular proliferate on the other side of the filter. Endothelial cells were seeded on one side of the filter before media-explants were laid on the other side of the filter. The confluent endothelium inhibited migration of SMCs through the filter pores. Media-explants were placed between two polycarbonate filters (pores 5 microns diameter). In this "sandwich" arrangement SMCs migrated through both filters, i.e., in both directions. The quantity of migrating and proliferating cells through both filters was almost identical. This suggests that there is no difference in the migratory and proliferative capacity of SMCs in the inner and outer layers in the media of arteries. To investigate the influence of the adventitia on medial SMCs, media-explants were placed between a lower (5 microns) and an upper (0.2 micron) filter. On the 0.2 micron filter adventitia-explants were laid above the media-explants. The 0.2 micron filter prevented migration of SMCs from the media-explant into the adventitia and migration of fibroblasts from the adventitia into the media. Interestingly, the adventitial tissue inhibited proliferation of SMCs at the abluminal and migration and proliferation at the luminal side of the media-explant; the number of cells migrating through the 5 microns pores at the luminal side was diminished, suggesting that the adventitial tissue has an antiproliferative influence on SMCs. Moreover, it was found that in media-explants near the filter with adventitia, the medial SMCs were in a better preserved condition than at the de-endothelialised luminal side. As a control, cultures consisting of media-explants were incubated without filters (i.e., explant organ cultures). The proliferates in the concavity (luminal side) exhibited a pattern of proliferating SMCs different from that of the cells at the abluminal convexity.(ABSTRACT TRUNCATED AT 400 WORDS)
在动脉粥样硬化和纤维肌性增生/病变的发展过程中，中膜中的平滑肌细胞（SMC），尤其是靠近管腔的平滑肌细胞被激活并迁移至内膜，在那里它们继续增殖，形成内膜增厚。迄今为止尚不清楚，毗邻外膜的SMC增殖能力较低，是因为它们是中膜SMC的一个特殊亚群，还是因为外膜发挥了抑制作用。因此，我们开发了一种体外系统，试图消除这种不确定性。从体外实验中得到了以下观察结果：将兔主动脉的中膜外植体置于孔径为5微米的聚碳酸酯滤膜上。SMC穿过这些孔，并在滤膜另一侧形成纤维肌性增生。在内膜外植体置于滤膜另一侧之前，先将内皮细胞接种在滤膜的一侧。汇合的内皮细胞抑制了SMC穿过滤膜孔的迁移。将内膜外植体置于两个聚碳酸酯滤膜（孔径5微米）之间。在这种“三明治”结构中，SMC向两个方向穿过两个滤膜。穿过两个滤膜迁移和增殖的细胞数量几乎相同。这表明动脉中膜内层和外层的SMC在迁移和增殖能力上没有差异。为了研究外膜对中膜SMC的影响，将内膜外植体置于下层（5微米）和上层（0.2微米）滤膜之间。在0.2微米滤膜上，将外膜外植体置于内膜外植体上方。0.2微米的滤膜阻止了SMC从内膜外植体迁移到外膜，以及成纤维细胞从外膜迁移到内膜。有趣的是，外膜组织抑制了内膜外植体近腔侧SMC的增殖以及远腔侧的迁移和增殖；穿过腔侧5微米孔的细胞数量减少，这表明外膜组织对SMC有抗增殖作用。此外，还发现，在靠近有外膜滤膜的内膜外植体中，中膜SMC的保存状况比去内皮的腔侧更好。作为对照，将由内膜外植体组成的培养物在无滤膜的情况下孵育（即外植体器官培养）。凹陷处（腔侧）的增生表现出与远腔侧凸起处细胞不同的SMC增殖模式。（摘要截选至400字）
