Phenotypic modulation of smooth muscle cells after arterial injury is associated with changes in the distribution of laminin and fibronectin.
Earlier in vitro studies suggest opposing roles of laminin and fibronectin in regulation of differentiated properties of vascular smooth muscle cells. To find out if this may also be the case in vivo, we used immunoelectron microscopy to study the distribution of these proteins during formation of intimal thickening after arterial injury. In parallel, cell structure and content of smooth muscle alpha-actin was analyzed. The results indicate that the cells in the normal media are in a contractile phenotype with abundant alpha-actin filaments and an incomplete basement membrane. Within 1 week after endothelial denudation, most cells in the innermost layer of the media convert into a synthetic phenotype, as judged by loss of actin filaments, construction of a large secretory apparatus, and destruction of the basement membrane. Some of these cells migrate through fenestrae in the internal elastic lamina and invade a fibronectin-rich network deposited on its luminal surface. Within another few weeks a thick neointima forms, newly produced matrix components replace the stands of fibronectin, and a basement membrane reappears. Simultaneously, the cells resume a contractile phenotype, recognized by disappearance of secretory organelles and restoration of alpha-actin filaments. These findings support the notion that laminin and other basement membrane components promote the expression of a differentiated smooth muscle phenotype, whereas fibronectin stimulates the cells to adopt a proliferative and secretory phenotype.
Thyberg
J
J
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
Blomgren
K
K
Roy
J
J
Tran
P K
PK
Hedin
U
U
D000199:Actins / Q000032:analysis; D000818:Animals; D004730:Endothelium, Vascular / Q000293:injuries; D005353:Fibronectins / Q000032:analysis*; D007797:Laminin / Q000032:analysis*; D008297:Male; D016253:Microscopy, Immunoelectron; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000293:injuries*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000199:Actins; D005353:Fibronectins; D007797:Laminin