Common signatures for gene expression in postnatal patients with patent arterial ducts and stented arteries

Abstract

The detailed molecular processes associated with postnatal remodelling of blood vessels are presently not understood. To characterize the response of the patients undergoing stenting of the patent arterial duct, we harvested samples of vascular tissue during surgical repair. Histological analysis of explanted ducts confirmed the patency of the ducts immediately after birth. As expected, a previously unstented duct that was examined 7 months after birth had become closed and ligamentous. Whole genome expression profiling of these samples showed that a large fraction, over 10%, of the gene sequences examined were expressed differentially between the samples taken from patients with open as opposed to the ligamentous duct. Interestingly, in 2 patients in whom closure was prevented by insertion of stents, one showed an expression profile that was similar to that of the patient initially having an unstented open duct, whereas the other was more closely related to the profile of the patient with a duct that had become ligamentous. Moreover, in 2 specimens obtained from patients with stented pulmonary arteries, a large fraction of the genes that were differentially expressed were identical to the pattern seen in the samples from the patients with open ducts. The gene regulation appeared to be independent of the nature of the respective malformations, and the site of implantation of the stents. These findings suggest that a set of differentially expressed genes are indicative for a transcriptional programme in neonatal remodelling of the arterial duct, which may also take place in patients in whom ductal closure is prevented by stents, or in those with stented pulmonary arteries. The differentially expressed genes included a significant number of extracellular matrix synthetic genes, and could therefore be predictive for vascular remodelling and neointimal formation.