Systemic Maternal Inflammation and Postnatal Hyperoxia Induces Early Life Cardiovascular Abnormalities in Mice

Abstract

BackgroundPremature infants have a higher incidence of heart failure, cardiac hypertrophy, and ventricular systolic dysfunction as young adults. The mechanism underlying these abnormalities likely include changes in proteins related to the structure and function of the heart including connexin 43, α myosin heavy chain (αMHC), and β myosin heavy chain (βMHC). microRNAs, including miR‐208a and miR‐208b, play a role in the regulation of myosin heavy chain expression. In adult mice, abnormalities in these proteins and microRNAs are triggered by perinatal inflammation and postnatal hyperoxia. These investigations test our hypothesis that systemic maternal inflammation and neonatal hyperoxia induce changes in the structural and conduction proteins of the mouse heart and are present in embryonic and newborn mice.MethodsPregnant C3H/HeN mice were injected on embryonic day 16 (E16) with intraperitoneal LPS (80 μg/kg) to induce perinatal inflammation or saline. Offspring were euthanized on E18 or day of life 1. Another group of offspring were placed into room air (RA) or 85% O2 for 7 days after birth prior to euthanizing. Total RNAs were isolated from frozen whole heart samples. RT‐PCR was used to examine mRNA expression of connexin 43, αMHC, and βMHC. RT‐PCR was also used to assess expression of miR‐208a and miR‐208b. Data were analyzed using an unpaired t‐test.ResultsMaternal LPS induces decreases in miR‐208b that are present at E18 (10‐fold, P<0.05) and persist at day of life 1 (15‐fold, P<0.05). At day of life 7, oxygen exposure induces a downregulation of miR‐208b (1.8‐fold, P<0.05) compared to room air. The inflammation‐exposed mice have significant decreases in miR‐208a (9‐fold, P<0.05) and αMHC mRNA (30,000‐fold, P<0.05) on day of life 1. By day of life 7, mice exposed to the combination of inflammation and hyperoxia have less (1.6‐fold, P<0.05) connexin 43 mRNA compared to the control mice; no changes in connexin 43 are seen at day of life 1 or at day of life 7 with exposure to inflammation without hyperoxia.ConclusionsMice exposed to perinatal inflammation and postnatal hyperoxia demonstrate changes in structural and conduction components of the heart that are evident at the time of birth.Support or Funding InformationNIH NICHD R01HD088033This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.