Journal article
Effects of Advancing Gestation and Non-Caucasian Race on Ductus Arteriosus Gene Expression
The Journal of pediatrics, Vol.167(5), pp.1033-1041.e2
11/2015
DOI: 10.1016/j.jpeds.2015.07.011
PMCID: PMC4661123
PMID: 26265282
Abstract
To identify genes affected by advancing gestation and racial/ethnic origin in human ductus arteriosus (DA).
We collected 3 sets of DA tissue (n = 93, n = 89, n = 91; total = 273 fetuses) from second trimester pregnancies. We examined four genes, with DNA polymorphisms that distribute along racial lines, to identify "Caucasian" and "non-Caucasian" DA. We used real time polymerase chain reaction to measure RNA expression of 48 candidate genes involved in functional closure of the DA, and used multivariable regression analyses to examine the relationships between advancing gestation, "non-Caucasian" race, and gene expression.
Mature gestation and non-Caucasian race are significant predictors for identifying infants who will close their patent DA when treated with indomethacin. Advancing gestation consistently altered gene expression in pathways involved with oxygen-induced constriction (eg, calcium-channels, potassium-channels, and endothelin signaling), contractile protein maturation, tissue remodeling, and prostaglandin and nitric oxide signaling in all 3 tissue sets. None of the pathways involved with oxygen-induced constriction appeared to be altered in "non-Caucasian" DA. Two genes, SLCO2A1 and NOS3, (involved with prostaglandin reuptake/metabolism and nitric oxide production, respectively) were consistently decreased in "non-Caucasian" DA.
Prostaglandins and nitric oxide are the most important vasodilators opposing DA closure. Indomethacin inhibits prostaglandin production, but not nitric oxide production. Because decreased SLCO2A1 and NOS3 expression can lead to increased prostaglandin and decreased nitric oxide concentrations, we speculate that prostaglandin-mediated vasodilation may play a more dominant role in maintaining the "non-Caucasian" patent DA, making it more likely to close when inhibited by indomethacin.
Details
- Title: Subtitle
- Effects of Advancing Gestation and Non-Caucasian Race on Ductus Arteriosus Gene Expression
- Creators
- Nahid Waleh - Biosciences Division, SRI International, Menlo Park, CAAnne Marie Barrette - Cardiovascular Research Institute and Department of Pediatrics, University of California San Francisco, San Francisco, CAJohn M Dagle - Department of Pediatrics, University of Iowa, Iowa City, IAAllison Momany - Department of Pediatrics, University of Iowa, Iowa City, IAChengshi Jin - Department of Neurology, University of California San Francisco, San Francisco, CANancy K Hills - Department of Neurology, University of California San Francisco, San Francisco, CAElaine L Shelton - Department of Pediatrics, Vanderbilt University, Nashville, TNJeff Reese - Department of Pediatrics, Vanderbilt University, Nashville, TNRonald I Clyman - Cardiovascular Research Institute and Department of Pediatrics, University of California San Francisco, San Francisco, CA. Electronic address: clymanr@peds.ucsf.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of pediatrics, Vol.167(5), pp.1033-1041.e2
- Publisher
- United States
- DOI
- 10.1016/j.jpeds.2015.07.011
- PMID
- 26265282
- PMCID
- PMC4661123
- ISSN
- 0022-3476
- eISSN
- 1097-6833
- Grant note
- R01 HL109199 / NHLBI NIH HHS T32 GM108540 / NIGMS NIH HHS HL109199 / NHLBI NIH HHS
- Language
- English
- Date published
- 11/2015
- Academic Unit
- Stead Family Department of Pediatrics; Epidemiology; Biochemistry and Molecular Biology; Neonatology
- Record Identifier
- 9984025270202771
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