PHENOTYPIC MODULATION OF SMOOTH-MUSCLE CELLS AFTER ARTERIAL INJURY ISASSOCIATED WITH CHANGES IN THE DISTRIBUTION OF LAMININ AND FIBRONECTIN

Earlier in vitro studies suggest opposing roles of laminin and fibrone ctin in regulation of differentiated properties of vascular smooth mus cle cells. To find out if this may also be the case in vivo, we used i mmunoelectron microscopy to study the distribution of these proteins d uring formation of intimal thickening after arterial injury. In parall el, cell structure and content of smooth muscle alpha-actin was analyz ed. The results indicate that the cells in the normal media are in a c ontractile phenotype with abundant alpha-actin filaments and an incomp lete basement membrane. Within 1 week after endothelial denudation, mo st cells in the innermost layer of the media convert into a synthetic phenotype, as judged by loss of actin filaments, construction of a lar ge secretory apparatus, and destruction of the basement membrane. Some of these cells migrate through fenestrae in the internal elastic lami na and invade a fibronectin-rich network deposited on its luminal surf ace. Within another few weeks a thick neointima forms, newly produced matrix components replace the strands of fibronectin, and a basement m embrane reappears. Simultaneously, the cells resume a contractile phen otype, recognized by disappearance of secretory organelles and restora tion 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 stimu lates the cells to adopt a proliferative and secretory phenotype.