Newby A C, Zaltsman A B
Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, UK.
Cardiovasc Res. 1999 Feb;41(2):345-60.
Endothelial activation and infiltration of monocyte macrophages are essential prerequisites for fibrous cap formation, which comprises proliferation and migration of smooth muscle cells and net matrix deposition. Macrophage foam cells and endothelium act as a source of growth factors and chemoattractants for smooth muscle cells. However, growth factors alone do not stimulate smooth muscle cell proliferation or migration. This requires, in addition, the remodelling of the extracellular matrix, at least partly mediated by metalloproteinases. In particular, loss of basement membrane components and contact with the interstitial matrix appears to be required to release a brake on proliferation and migration exerted by the basement membrane. Unless there is a change in the phenotype of macrophages in advanced lesions, it is not clear why fibrous cap destruction rather than formation should take place in macrophage-rich shoulder regions of plaques. Impaired cap formation caused by smooth muscle senescence, mummification and propensity to apoptosis may be as important as increased cap destruction in promoting plaque rupture.
内皮细胞活化和单核巨噬细胞浸润是纤维帽形成的重要前提条件，纤维帽形成包括平滑肌细胞的增殖和迁移以及净基质沉积。巨噬细胞泡沫细胞和内皮细胞作为平滑肌细胞生长因子和趋化因子的来源。然而，仅生长因子并不能刺激平滑肌细胞增殖或迁移。此外，这还需要细胞外基质重塑，至少部分由金属蛋白酶介导。特别是，似乎需要基底膜成分的丧失以及与间质基质的接触，以解除基底膜对增殖和迁移的抑制作用。除非晚期病变中巨噬细胞的表型发生改变，否则尚不清楚为何在富含巨噬细胞的斑块肩部区域会发生纤维帽破坏而非形成。平滑肌衰老、木乃伊化和凋亡倾向导致的帽形成受损，在促进斑块破裂方面可能与帽破坏增加同样重要。
