Abstract 12927: The Human Ductus Arteriosus Smooth Muscle Cell Transcriptome Indicates a Central Role for Mitochondria in Postnatal Oxygen Sensing

• Published in: Circulation (New York, N.Y.) N.Y.), 2021-11, Vol.144 (Suppl_1), p.A12927-A12927
• Main Authors: Bentley, Rachel E, Hindmarch, Charles C, Dunham-Snary, Kimberly J, Mewburn, Jeffrey, Snetsinger, Brooke, Thebaud, Arthur, Lima, Patricia, Thebaud, B, Archer, Stephen L
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.144.suppl_1.12927

IntroductionThe ductus arteriosus (DA) connects the fetal pulmonary artery and aorta, diverting placentally oxygenated blood from the developing lungs to the systemic circulation. The DA constricts in response to increased oxygen (O2) immediately post-partum, resulting in functional DA closure, with anatomic closure ensuing within the first days of life. Failure of DA closure results in patent ductus arteriosus (PDA), a common complication of extreme preterm birth. The DA response to O2, though modulated by the endothelium, is intrinsic to DA smooth muscle cells (DASMC). DA constriction is mediated by mitochondria-derived reactive oxygen species, which increase in proportion to PaO2. The molecular signature of the DASMC response to O2 is not well understood. Methods & ResultsDASMC were isolated from DA obtained from 10 infants at the time of congenital heart surgery. Cells were purified by flow cytometry, negatively sorted to eliminate fibroblasts (CD90+) or endothelial cells (CD31+). DASMC purity was confirmed by α-smooth muscle actin staining. Cells were grown for 96 hours in hypoxia (2.5% O2) or normoxia (19% O2) and confocal calcium imaging confirmed O2-responsiveness of all cell linesO2 exposure increased intracellular calcium 18.1%±4.4% and decreased cell length 27%±1.5% relative to hypoxic baseline. RNA sequencing (Seq) of the cells grown in hypoxia and normoxia revealed significant regulation of 1344 genes (corrected p