Aoyagi M, Yamamoto M, Azuma H, Nagashima G, Niimi Y, Tamaki M, Hirakawa K, Yamamoto K
Department of Cell Biology, Tokyo Metropolitan Institute of Gerontology, Japan.
Histochem Cell Biol. 1998 Feb;109(2):97-102. doi: 10.1007/s004180050206.
Extracellular matrix-degrading enzymes may play a key role in vascular remodeling after arterial wall injury. We investigated the immunolocalization of matrix metalloproteinases (MMPs) in rabbit carotid arteries after balloon denudation. Positive immunostaining for MMP-1, -2, -3, and -9 appeared through the neointima 1 week after balloon denudation. The localization of immunopositive smooth muscle cells (SMCs) for MMP- 1, -3, and -9, particularly for MMP-9, was almost similar to that of replicative SMCs and became confined to the luminal surface layer of the neointima at later time periods. However, MMP-2-positive SMCs appeared also in the basal layer of the neointima at 2 weeks, increased at 4 weeks, and then totally occupied the neointima at 6 weeks. The MMP-2-positive SMCs in the basal layer of the neointima at 4 and 6 weeks were negative for proliferation-associated antigens and were surrounded by extracellular matrix proteins. Our results suggest that all MMPs act in coordination to promote replication and migration of SMCs in the earlier phases of neointimal formation and that MMP-2 independently contributes to the later stages by facilitating the migration but not replication of SMCs from the media to the intima.
细胞外基质降解酶可能在动脉壁损伤后的血管重塑中起关键作用。我们研究了球囊剥脱术后兔颈动脉中基质金属蛋白酶（MMPs）的免疫定位。球囊剥脱术后1周，MMP - 1、- 2、- 3和- 9出现阳性免疫染色。MMP - 1、- 3和- 9免疫阳性平滑肌细胞（SMCs）的定位，尤其是MMP - 9，与增殖性SMCs的定位几乎相似，并在后期局限于新生内膜的腔表面层。然而，MMP - 2阳性SMCs在2周时也出现在新生内膜的基底层，4周时增加，然后在6周时完全占据新生内膜。4周和6周时新生内膜基底层的MMP - 2阳性SMCs增殖相关抗原呈阴性，并被细胞外基质蛋白包围。我们的结果表明，所有MMPs在新生内膜形成的早期阶段协同作用以促进SMCs的增殖和迁移，并且MMP - 2通过促进SMCs从介质向内膜的迁移而非增殖，独立地在后期阶段发挥作用。
