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We previously showed that experimental IUGR impairs angiogenesis; however, mechanisms that impair pulmonary artery endothelial cell (PAEC) function are uncertain. The NF-\u03baB pathway promotes vascular growth in the developing mouse lung, and we hypothesized that IUGR disrupts NF-\u03baB-regulated proangiogenic targets in fetal PAEC. PAECs were isolated from the lungs of control fetal sheep and sheep with experimental IUGR from an established model of chronic placental insufficiency. Microarray analysis identified suppression of NF-\u03baB signaling and significant alterations in extracellular matrix (ECM) pathways in IUGR PAEC, including decreases in collagen 4\u03b11 and laminin \u03b14, components of the basement membrane and putative NF-\u03baB targets. In comparison with controls, immunostaining of active NF-\u03baB complexes, NF-\u03baB-DNA binding, baseline expression of NF-\u03baB subunits p65 and p50, and LPS-mediated inducible activation of NF-\u03baB signaling were decreased in IUGR PAEC. Although pharmacological NF-\u03baB inhibition did not affect angiogenic function in IUGR PAEC, angiogenic function of control PAEC was reduced to a similar degree as that observed in IUGR PAEC. These data identify reductions in endothelial NF-\u03baB signaling as central to the disrupted angiogenesis observed in IUGR, likely by impairing both intrinsic PAEC angiogenic function and NF-\u03baB-mediated regulation of ECM components necessary for vascular development. These data further suggest that strategies that preserve endothelial NF-\u03baB activation may be useful in lung diseases marked by disrupted angiogenesis such as IUGR. <\/jats:p>","DOI":"10.1152\/ajplung.00052.2018","type":"journal-article","created":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T12:00:30Z","timestamp":1525348830000},"page":"L348-L359","source":"Crossref","is-referenced-by-count":18,"title":["Intrauterine growth restriction decreases NF-\u03baB signaling in fetal pulmonary artery endothelial cells of fetal sheep"],"prefix":"10.1152","volume":"315","author":[{"given":"R. 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