Fibrous cap formation or destruction - the critical importance of vascularsmooth muscle cell proliferation, migration and matrix formation

Endothelial activation and infiltration of monocyte macrophages are essenti al prerequisites for fibrous cap formation, which comprises proliferation a nd migration of smooth muscle cells and net matrix deposition. Macrophage f oam cells and endothelium act as a sourer of growth factors and chemoattrac tants for smooth muscle cells. However, growth factors alone do not stimula te smooth muscle cell proliferation or migration. This requires, in additio n, the remodelling of the extracellular matrix, at least partly mediated by metalloproteinases. Tn particular, loss of basement membrane components an d contact with the interstitial matrix appears to be required to release a brake on proliferation and migration exerted by the basement membrane. Unle ss there is a change in the phenotype of macrophages in advanced lesions, i t is not clear why fibrous cap destruction rather than formation should tak e place in macrophage-rich shoulder regions of plaques. Impaired cap format ion caused by smooth muscle senescence, mummification and propensity to apo ptosis may be as important as increased cap destruction in promoting plaque rupture. (C) 1999 Elsevier Science B.V. All rights reserved.