Plenz G, Dorszewski A, Breithardt G, Robenek H
Department of Cell Biology and Ultrastructure Research, Section of Molecular Cardiology, Institute for Arteriosclerosis Research at the University of Muenster, Germany.
Arterioscler Thromb Vasc Biol. 1999 May;19(5):1201-9. doi: 10.1161/01.atv.19.5.1201.
This study presents an analysis of the expression of type VIII collagen mRNA in response to cholesterol diet and balloon injury in the rabbit iliac artery. The design of the animal experiments was as follows: 28 male New Zealand White rabbits were divided into the 3 different treatment groups. Group 1 received regular chow; group 2 was fed with a 1% cholesterol diet for 6 weeks and normal chow for 5 weeks; and group 3 underwent balloon injury, then 6 weeks of a 1% cholesterol diet, which was followed by 5 weeks of normal chow. The expression pattern of type VIII collagen mRNA was compared with that of the fibrillar collagen types I and III, transforming growth factor-beta1, a factor known to exert the most potent stimulatory effect on collagen synthesis in vitro, and matrix metalloproteinase 1, a collagen-degrading enzyme. The cholesterol diet resulted in an upregulation of type VIII collagen, fibrillar collagens, transforming growth factor-beta1, and matrix metalloproteinase I in the adventitia. Although the number of type VIII collagen mRNA-expressing cells in the media increased, no significant difference in overall expression levels was detectable by northern blot analysis. The ratio of medial smooth muscle cells expressing type VIII collagen mRNA to those expressing type I and type III collagen mRNA (CVIII:CI:CIII) changed from 1:1.88:0.03 in the normal media to 1:0.78:0.29. When cholesterol feeding was preceded by balloon injury, type VIII collagen mRNA expression concomitant with the fibrillar collagens was further upregulated over and above that level reported after cholesterol diet alone. In general, low levels of transforming growth factor-beta1 mRNA correlated with high expression of matrix metalloproteinase I. Our study indicates that a cholesterol diet resulted in a balanced reorganization of the collagen composition but did not result in marked collagen accumulation. This may provide an extracellular environment that favors migration and proliferation processes during early atherogenesis. It also demonstrates that type VIII collagen is highly expressed and deposited at later stages, and this may be linked to processes such as tissue reorganization during vascular repair and plaque stabilization.
本研究分析了兔髂动脉中VIII型胶原mRNA在胆固醇饮食和球囊损伤作用下的表达情况。动物实验设计如下：28只雄性新西兰白兔被分为3个不同的治疗组。第1组给予常规饲料；第2组先喂1%胆固醇饮食6周，再喂正常饲料5周；第3组先进行球囊损伤，然后喂1%胆固醇饮食6周，之后再喂正常饲料5周。将VIII型胶原mRNA的表达模式与I型和III型纤维状胶原、转化生长因子-β1（已知在体外对胶原合成具有最强刺激作用的因子）以及基质金属蛋白酶1（一种胶原降解酶）的表达模式进行比较。胆固醇饮食导致外膜中VIII型胶原、纤维状胶原、转化生长因子-β1和基质金属蛋白酶I上调。尽管中膜中表达VIII型胶原mRNA的细胞数量增加，但通过Northern印迹分析未检测到总体表达水平有显著差异。中膜中表达VIII型胶原mRNA的平滑肌细胞与表达I型和III型胶原mRNA的平滑肌细胞的比例（CVIII:CI:CIII）从正常中膜的1:1.88:0.03变为1:0.78:0.29。当在球囊损伤后给予胆固醇喂养时，与纤维状胶原相伴的VIII型胶原mRNA表达比仅给予胆固醇饮食后报道的水平进一步上调。总体而言，低水平的转化生长因子-β1 mRNA与基质金属蛋白酶I的高表达相关。我们的研究表明，胆固醇饮食导致胶原组成的平衡重组，但未导致明显的胶原积累。这可能提供了一个有利于早期动脉粥样硬化形成过程中迁移和增殖过程的细胞外环境。研究还表明，VIII型胶原在后期高度表达并沉积，这可能与血管修复和斑块稳定过程中的组织重组等过程有关。
