Academic Journal

Long Term Hypoxia Reduces Levels of Oxylipins in Pulmonary Arteries and Venous Plasma of Fetal Sheep

التفاصيل البيبلوغرافية
العنوان: Long Term Hypoxia Reduces Levels of Oxylipins in Pulmonary Arteries and Venous Plasma of Fetal Sheep
المؤلفون: Lopez, Vanessa, La Frano, Michael, Bosviel, Remy, Hillman, Tyler C, Newman, John, Thorpe, Richard, Fiehn, Oliver, Zhang, Lubo, Wilson, Sean M
المساهمون: National Institutes of Health, American Physiological Society
المصدر: The FASEB Journal ; volume 33, issue S1 ; ISSN 0892-6638 1530-6860
بيانات النشر: Wiley
سنة النشر: 2019
المجموعة: Wiley Online Library (Open Access Articles via Crossref)
الوصف: High‐altitude long term hypoxia (LTH) during gestation compromises the development and function of the pulmonary vasculature in the fetus and later in the newborn. This may manifest as fetal growth restriction as well as pulmonary hypertension following birth. While the physiological regulation regarding the effects of hypoxia are well‐known, the dysregulation that occurs at the cellular and molecular level is not yet completely understood. Exploring the effects of LTH using a metabolomic approach is advantageous in deciphering the etiology associated with the development of disease. LTH is well regarded for inducing oxidative stress and causing inflammation. A number of possible regulators associated with LTH stress include oxylipins and endocannabinoids, products of polyunsaturated fatty acid (PUFA) oxidation. We hypothesized that high‐altitude LTH would reduce the levels of oxylipins and endocannabinoids of pulmonary arteries and plasma in fetal sheep. To test the hypothesis, we obtained samples of plasma and pulmonary arteries from fetal normoxic and hypoxic sheep raised at 3,800 m. altitude starting on gestation day 30. Metabolite levels were quantified using ultra performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS). Chemical similarity enrichment analyses and visualization by complex pathway analyses was performed on the datasets. Our results support our hypothesis that select oxylipin concentrations were diminished in both venous plasma and pulmonary arteries. Omega‐3 PUFAs alpha linolenic acid (ALA) and eicosapentaenoic acid (EPA) were reduced in both plasma and pulmonary arteries. 15‐HEPE and 12‐HEPE, derivatives of EPA and important anti‐inflammatory mediators, were also significantly reduced by LTH in plasma and pulmonary arterial samples from fetal animals. We believe that our studies provide insight toward identifying key biomarkers of LTH stress that will afford effective and prompt diagnosis of the neonate's physiological response. This is important when it comes to treating ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1096/fasebj.2019.33.1_supplement.550.5
الاتاحة: http://dx.doi.org/10.1096/fasebj.2019.33.1_supplement.550.5
Rights: http://onlinelibrary.wiley.com/termsAndConditions#vor
رقم الانضمام: edsbas.6B82C2F
قاعدة البيانات: BASE
الوصف
DOI:10.1096/fasebj.2019.33.1_supplement.550.5