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RAGE targeting ameliorates responses to antenatal SHS exposure
Author(s) -
Hirschi K M,
Tsai K YF,
Clark C,
Hutchinson T,
Hall P,
Arroyo J A,
Reynolds P R
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.496.23
Subject(s) - medicine , offspring , glycation , fetus , rage (emotion) , receptor , placenta , lung , kidney , endocrinology , pregnancy , andrology , physiology , biology , neuroscience , genetics
Secondhand tobacco smoke (SHS) exposure during pregnancy is associated with increased health complications to both mother and fetus. Exposure can lead to anomalous organ development, increased blood pressure, and decreased metabolism. Receptors for advanced glycation end‐products (RAGE) are pro‐inflammatory transmembrane receptors increased by SHS. Inhibition of RAGE signaling by semisynthetic glycosaminoglycan ethers (SAGEs) has been shown to reduce inflammation in the adult and improve fetal birthweight. We tested the hypothesis that in vivo inhibition of RAGE by SAGEs during antenatal SHS exposure improves postnatal health of the offspring. Pregnant Balb/C mice were exposed to SHS alone or SHS + SAGEs from embryonic day (E) 14 to E17. RAGE expression and general measures of development were assessed in the offspring at four and twelve weeks of age. Statistical analysis was completed using nonparametric Mann‐Whitney testing. Antenatal SHS resulted in the following at four weeks of age: 1) increased body weight (p =0.0118) which was reduced to basal levels when treated with SAGEs; 2) decreased heart (p=0.0017) and kidney (p=0.0001) weights and improvement with concurrent SAGEs; 3) increased neonatal blood pressure and further increases with SAGEs; 4) increased expression of RAGE in kidney (p=0.0090), heart (p=.044), and lung (p=0.0022) with significant recovery with SAGEs; 5) mild reduction in alveolar surface area via MLI assessment and airspace normalization with SAGE treatment. No significant differences were apparent for any metric at 12 weeks of age. We conclude that inhibition of RAGE protects against fetal health complications following antenatal SHS exposure. Our results further suggest that there is a correlation between RAGE expression and a plausible role for RAGE signaling in key organs following maternal SHS exposure. These studies provide insight into tobacco‐mediated heath compromise and implicate possible avenues worth pursuing further in the alleviation of symptoms of antenatal SHS exposure. Support or Funding Information This work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI, PRR and JAA) and a BYU Mentoring Environment Grant (JAA and PRR). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .