De Mey J G, Uitendaal M P, Boonen H C, Schiffers P M, Fazzi G E
Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.
Blood Vessels. 1991;28(5):372-85. doi: 10.1159/000158884.
To evaluate whether intravascular phenomena contribute to local differences in growth responses of the arterial wall, we evaluated responses to organoid culture in a broad variety of arterial preparations. Arterial segments were isolated from adult, normotensive rats, sympathectomized, denuded from endothelium, and suspended in medium supplemented with serum. As judged from the nuclear incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdUrd), this induced a transient stimulation of DNA synthesis in only a fraction of the arterial smooth muscle cells in all types of arteries. This intramedial DNA synthesis was more marked in renal arteries than in carotid arteries or aortae and was least pronounced in main pulmonary, femoral, and superior mesenteric artery and in mesenteric resistance-sized arteries. Organoid culture of isolated arteries did not increase the cross-sectional area of the media or the number of medial cells. It rather resulted in proliferation of smooth-muscle-like cells outside the media. In addition, smooth-muscle-like cells migrated out of the isolated arterial segments during culture. The rate of proliferation of these isolated cells did not differ between large arteries of different anatomical origin. However, isolated cells derived from mesenteric resistance arteries proliferated at a rate that was 4 times slower than that of large artery cells. The presence of endothelium significantly reduced medial DNA synthesis in carotid and renal artery segments, but not in mesenteric resistance-sized preparations. These data indicate that growth responses of the arterial wall differ quantitatively with the anatomical location and branching order of the vascular segment. In addition to the regional heterogeneity of endothelial effects on mitogenic responses of arterial smooth muscle, this seems to be due to regional differences in the susceptibility of arterial smooth muscle to exogenous growth factors. In this respect, we speculate that subsets of growth-resistant and growth-prone arterial smooth muscle cells could be heterogeneously distributed over the arterial tree.
为了评估血管内现象是否导致动脉壁生长反应的局部差异，我们在多种动脉制剂中评估了对类器官培养的反应。从成年正常血压大鼠分离动脉段，进行交感神经切除术，去除内皮，然后悬浮于补充有血清的培养基中。根据胸苷类似物5-溴-2'-脱氧尿苷（BrdUrd）的核掺入判断，这仅在所有类型动脉的一部分动脉平滑肌细胞中诱导了DNA合成的短暂刺激。这种中膜内DNA合成在肾动脉中比在颈动脉或主动脉中更明显，而在主肺动脉、股动脉和肠系膜上动脉以及肠系膜阻力大小的动脉中最不明显。分离动脉的类器官培养并未增加中膜的横截面积或中膜细胞数量。相反，它导致中膜外平滑肌样细胞的增殖。此外，在培养过程中，平滑肌样细胞从分离的动脉段中迁移出来。这些分离细胞的增殖速率在不同解剖起源的大动脉之间没有差异。然而，来自肠系膜阻力动脉的分离细胞的增殖速率比大动脉细胞慢4倍。内皮的存在显著降低了颈动脉和肾动脉段的中膜DNA合成，但在肠系膜阻力大小的制剂中没有降低。这些数据表明，动脉壁的生长反应在数量上因血管段的解剖位置和分支顺序而异。除了内皮对动脉平滑肌有丝分裂反应的区域异质性外，这似乎还归因于动脉平滑肌对外源生长因子敏感性的区域差异。在这方面，我们推测抗生长和易生长的动脉平滑肌细胞亚群可能在动脉树中呈异质性分布。
