Plasma exosome derived MiR221 as a driver of long term hypoxia induced aberrations in pulmonary arterial phenotype in fetal sheep

• DOI: 10.1152/physiol.2023.38.s1.5796248
• Publication Date: 2023-05-29T14:52:22Z
• Authors: Julio Sierra; Ciprian Gheorghe; Eric Leslie; Chiranjib Dasgupta; Alex Brito; Lubo Zhang; John Newman; Michael La Frano; Oliver Fiehn; Sean Wilson
• Keywords: Hypoxia; Hypoxic pulmonary vasoconstriction

Pregnancy at high altitude (> 2500 meters) reduces oxygenation to the fetus (i.e., gestational hypoxia). The low causes abnormal fetal lung development, with pulmonary arteries becoming thicker and dysfunctional. Associated these structural functional aberrations there is an increased risk of hypertension, intractable disease that increases infant mortality. Our previous work using a high-altitude sheep model shows has vascular remodeling, heart dysfunction, endoplasmic reticulum stress, metabolomic alterations inflammatory responses. To better understand relationships between inflammation, development arterial we used multi-omic approach examining plasma exosomes in exposed (3801 for most pregnancy (110+ days out 138-141 pregnancy). We sought role exosome derived microRNA as drivers malformations ingenuity pathway analysis exosomal combination metabolites proteins. Transcriptomic showed miR221 was upregulated exosomes. Pathway identified - AKT dependent signaling axis candidate downregulates expression smooth muscle myosin heavy chain 11 multiple collagen isoforms. Although needs validation, predictions show changes are likely coordinated discrete proteins coupled phenotype wall structure. These effects predicted be linked associated hypertension response hypoxia. This supported by National Institutes Health Grants R03HD098477, West Coast Metabolomics Center Pilot Project, NIH R01HL155295, R01HL149608, P01HD083132, U24DK097154. Additional support provided USDA JWN [Intramural Projects 2032-51530-022-00D, 2032-51530-025-00D]. content solely responsibility authors does not represent official views or USDA. equal opportunity employer provider. full abstract presented American Physiology Summit 2023 meeting only available HTML format. There no additional versions this abstract. involved peer review process.