Rasmussen L M, Wolf Y G, Ruoslahti E
Cancer Research Center, La Jolla Cancer Research Foundation, California, USA.
Am J Pathol. 1995 Oct;147(4):1041-8.
The arterial response to injury is characterized by a short period of increased proliferation and migration of vascular smooth muscle cells, followed by an extended period of extracellular matrix accumulation in the intima. Transforming growth factor-beta (TGF-beta) has been implicated as a causative factor in the formation of extracellular matrix in this process, which leads to progressive thickening of the intima, known as intimal hyperplasia. In vitro analysis of vascular smooth muscle cells harvested from normal rat aortas and from aortas injured 14 days earlier showed that both types of cells attached equally well to culture dishes but that the initial spreading of the cells was increased in cells derived from injured vessels. Cells from the injured arteries produced more fibronectin and proteoglycans into the culture medium than the cells from normal arteries and contained more TGF-beta 1 mRNA. TGF-beta 1 increased proteoglycan synthesis by normal smooth muscle cells, and the presence of a neutralizing anti-TGF-beta 1 antibody reduced proteoglycan synthesis by the cells from injured arteries in culture. Fibronectin synthesis was not altered by these treatments. These results indicate that the accumulation of extracellular matrix components in neointimal lesions is at least partially caused by autocrine TGF-beta activity in vascular smooth muscle cells.
动脉对损伤的反应特征为血管平滑肌细胞增殖和迁移增加的短期阶段，随后是内膜细胞外基质积累的长期阶段。转化生长因子-β（TGF-β）被认为是该过程中细胞外基质形成的致病因素，这会导致内膜逐渐增厚，即内膜增生。对从正常大鼠主动脉以及14天前受伤的主动脉中采集的血管平滑肌细胞进行的体外分析表明，这两种类型的细胞在培养皿上的附着情况相同，但来自受伤血管的细胞其初始铺展有所增加。与正常动脉来源的细胞相比，受伤动脉来源的细胞向培养基中分泌更多的纤连蛋白和蛋白聚糖，且含有更多的TGF-β1 mRNA。TGF-β1可增加正常平滑肌细胞的蛋白聚糖合成，而加入中和性抗TGF-β1抗体可减少培养的受伤动脉来源细胞的蛋白聚糖合成。这些处理对纤连蛋白合成没有影响。这些结果表明，新生内膜病变中细胞外基质成分的积累至少部分是由血管平滑肌细胞中的自分泌TGF-β活性引起的。
