CHANGES IN ENDOTHELIAL-CELL AND SMOOTH-MUSCLE CELL INTEGRIN EXPRESSION DURING CLOSURE OF THE DUCTUS-ARTERIOSUS - AN IMMUNOHISTOCHEMICAL COMPARISON OF THE FETAL, PRETERM NEWBORN, AND FULL-TERM NEWBORN RHESUS-MONKEY DUCTUS

Anatomical closure of the ductus arteriosus requires normally quiescen t luminal endothelial cells and medial smooth muscle cells to migrate into the subendothelial space forming intimal mounds that eventually c oalesce and occlude the vessel's lumen. The migration of endothelial c ells and smooth muscle cells requires the presence of integrin recepto rs that interact with the surrounding matrix. We used immunohistochemi cal staining to examine the repertoires of integrins expressed by endo thelial cells and smooth muscle cells during postnatal closure of the ductus arteriosus in full-term and preterm rhesus monkeys. In the feta l ductus, luminal endothelial cells have a limited repertoire of integ rins. During postnatal ductus closure, luminal endothelial cells, of b oth term and preterm monkeys, change their phenotype and express the f ull repertoire of integrins found on growing capillary endothelial cel ls (alpha(1) beta(1), alpha(2) beta(1), alpha(3) beta(1), alpha(6) bet a(1), alpha(v) beta(1), alpha(6) beta(4), and alpha(v) beta(5)). Simil arly, during ductus closure, smooth muscle cells of both term and pret erm monkeys expand their integrin repertoire to include the alpha(5) b eta(1) and alpha(v) beta(3) integrins; these two integrins have been s hown to be essential for smooth muscle cell migration in vitro. These changes in integrin profile occur at the same time the endothelial and smooth muscle cells invade their neighboring compartments. In contras t, preterm monkeys with a persistently patent ductus lumen fail to dev elop these changes in integrin expression and fail to develop neointim al mounds, No evidence of intimal thickening occurs in the absence of changes in integrin expression, Therefore, endothelial cells and smoot h muscle cells change phenotypes to produce the intimal thickening req uired for ductus closure.