Gene expression in sheep carotid arteries: major changes with maturational development

Abstract

With development from immature fetus to near-term fetus, newborn, and adult, the cerebral vasculature undergoes a number of fundamental changes. Although the near-term fetus is prepared for a transition from an intra- to extra-uterine existence, this is not necessarily the case with the premature fetus, which is more susceptible to cerebrovascular dysregulation. In this study, we tested the hypothesis that the profound developmental and age-related differences in cerebral blood flow are associated with significant underlying changes in gene expression. With the use of oligonucleotide microarray and pathway analysis, we elucidated significant changes in the transcriptome with development in sheep carotid arteries. As compared with adult, we demonstrate a U-shaped relationship of gene expression in major cerebrovascular network/pathways during early life, e.g., the level of gene expression in the premature fetus and newborn is considerably greater than that of the near-term fetus. Specifically, cell proliferation, growth, and assembly pathway genes were upregulated during early life. In turn, as compared with adult, mitogen-activated protein kinase-extracellular regulated kinase, actin cytoskeleton, and integrin-signaling pathways were downregulated during early life. In cranial vascular smooth muscle, highly significant changes occur in important cellular and signaling pathways with maturational development.