Investigating the Impact of Circulating miRNAs on Cardiovascular System Remodeling During Pregnancy

Abstract

During pregnancy, women undergo significant remodeling of their cardiovascular system, a complex process involving various physiological adaptations to ensure an adequate blood supply to the developing fetus. An intriguing area of research focuses on the role of circulating microRNAs, particularly the primate-specific chromosome 19 miRNA cluster (C19MC) and the rodent-specific chromosome 2 miRNA cluster (C2MC), both of which exhibit high expression levels in the placenta. Extracellular vesicles, such as exosomes, play a crucial role in intercellular communication and may carry microRNAs that contribute to the physiological changes observed during pregnancy. However, the influence of circulating C19MC and C2MC microRNAs on maternal cardiovascular system remodeling remains unexplored. We hypothesized that the increased levels of circulating C2MC or C19MC microRNAs during pregnancy might play a role in the maternal cardiovascular system adaptations. To investigate this hypothesis, we conducted a study to determine whether circulating exosomes during pregnancy lead to elevated expression levels of C19MC or C2MC microRNAs in various organs, including the heart, kidney, liver, spleen, lungs, and brain. In our investigation, we utilized three distinct mouse models: wild-type (WT) mice expressing only C2MC, C2MC knock-out (KO) mice, and a novel humanized mouse model, which combined C2MC KO with either a single or double copy of the human C19MC. We extracted total RNA from the organs of these mice and performed cDNA synthesis. Subsequently, we measured the expression levels of two representative microRNAs, miR-517a and miR-466a, corresponding to C19MC and C2MC, respectively, in the organs of pregnant and non-pregnant mice using TaqMan RT-qPCR. Our results indicated no significant differences in the expression levels of miR-517a and miR-466a when normalized to the housekeeping gene snoRNA-202 across different organs in pregnant and non-pregnant mice. To comprehensively assess the expression patterns of all microRNAs within the C19MC and C2MC clusters in various organs of pregnant and non-pregnant mice, further investigation with a larger sample size and small RNA-Seq analysis is warranted. This approach will enable us to explore a broader spectrum of microRNAs and potentially identify specific candidates that may play a crucial role in the essential physiological process of maternal cardiovascular system remodeling. This study is supported by USF Cardiovascular Summer Undergraduate Research Fellowship (SURF) sponsored by the American Heart Association. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.