EXPRESSION AND LOCALIZATION OF TROPOELASTIN MESSENGER-RNA IN THE DEVELOPING BOVINE PULMONARY-ARTERY IS DEPENDENT ON VASCULAR CELL PHENOTYPE

During vascular development, the expression of tropoelastin (TE) messe nger ribonucleic acid (mRNA) has been shown to be time dependent and t o form complex patterns along the longitudinal and radial arterial axe s. The factors contributing to these patterns of TE expression are not known, but it has been suggested that they reflect phenotypic changes in developing smooth muscle cells (SMC). In order to examine a possib le correlation between the developmental state of the SMC and TE expre ssion during lung vascular development, we localized and assessed rela tive TE mRNA expression in the developing bovine main pulmonary artery (PA), and correlated the observed patterns of TE expression to change s in SMC phenotype as determined by the expression of various developm entally related SMC proteins. Further, because TE expression can be mo dulated by physical forces such as pressure, fetal PA TE expression wa s evaluated with regard to changes in fetal arterial pressure. We foun d that expression of TE mRNA exhibited a biphasic pattern during fetal development. In early gestation, expression was noted throughout the entire PA wall; at midgestation, expression was markedly decreased in the outer wall but maintained in the inner vascular media; at late ges tation, reexpression was observed throughout the entire PA wall, albei t in a heterogeneous pattern. Immunohistochemical studies showed that the decrease in SMC TE expression during midgestation coincided with t he acquisition of SMC-specific proteins such as smooth muscle myosin h eavy chains and desmin. The reexpression of TE late in gestation occur red in these ''differentiated'' SMC and was temporally associated with a large increase in arterial pressure shown to occur in late gestatio n. In addition, we identified an SMC population defined by its immunor eactivity to the muscle-specific cytoskeletal protein meta-vinculin th at did not express TE mRNA either during fetal PA development or postn atally when PA hypertension was induced. We conclude that both the dev elopmental state of the SMC and hemodynamic forces correlate with the pattern of PA TE mRNA expression during pulmonary vascular development . Further, a subpopulation of SMC defined by meta-vinculin expression exists in the fetal and neonatal bovine vascular wall and does not exp ress detectable levels of TE mRNA regardless of vascular pressure.