Diversity of the synthetic-state smooth-muscle cells proliferating in mechanically and hemodynamically injured rabbit arteries.

Vascular smooth muscles contain at least three types of developmentally regulated myosin heavy-chain (MHC) isoforms; SM1, SM2, and SMemb. By investigating the expression of the three MHC isoforms, we previously demonstrated in rabbits that smooth muscles proliferating in the neointima of arterio- and atherosclerotic lesions regain an "embryonic" phenotype. In the present study, we examined if neointimal cells are morphologically similar to embryonal smooth muscles and if dedifferentiation of neointimal smooth muscles is a reversible process. Vascular injury was produced in rabbits either by endothelial cell denudation of the aorta or by poststenotic dilation of the carotid artery. We have demonstrated in this study that the proliferating neointimal cells expressed SM1 and SMemb, but not SM2, indicating smooth muscles of an "embryonic" phenotype. The dedifferentiation of neointimal smooth muscles was found to be reversible; at 4 to 8 weeks after injury, a majority of the cells reexpressed both SM1 and SM2, but not SMemb. By electron microscopy, we have revealed smooth-muscle phenotypes determined by MHC isoforms to correspond to the morphologic phenotypes as an increase in membranous organelles, and a decrease in myofilaments was associated with the reexpression of SMemb. Interestingly, we also found that in the medial wall at 4 to 8 weeks after ballooning injury, a number of SM1-negative cells proliferated rapidly, replacing normal smooth muscles. These cells were negative against SM1 and SM2 but positive for SMemb. These SM1-negative cells contained abundant membranous organelles and few myofilaments. These cells did not express SM1 or SM2 even after 8 weeks postinjury. We conclude from these results that the proliferating synthetic-type smooth muscles after vascular injury are composed of SM1-positive cells that are morphologically similar to embryonal smooth muscle and that maintain ability to redifferentiate, and SM1-negative cells that contain few myofilaments and remain dedifferentiated.