Differential Expression of Angiogenic miRNA hsa-miR-144-3p and hsa-miR-1260a Supports the Hepatic Factor Concept of Pathogenesis of Pulmonary Arteriovenous Malformations in Humans
Vettukattil, Tejas J.
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Similarities in the pathogenesis of Pulmonary Arteriovenous Malformations (PAVMs) in both Hepatopulmonary Syndrome (HPS), and as a result of various congenital heart disease interventions, has lead researchers to believe that an unknown factor necessary for healthy vasculature is present in hepatic effluent flow. It has been postulated that this so-called ‘Hepatic Factor’ may be one or many micro RNA, due to the known function of miRNA in post transcriptional gene expression. This study explored the Hepatic Factor miRNA hypothesis by extracting total RNA from human blood samples via spin column extraction, and quantifying differential expression of possible Hepatic Factor candidates via qPCR. miRNA were selected based on a combination of preliminary studies conducted by the lab, and independent literature. Seven human miRNA were tested for, in addition to two C.elegans miRNA spike-in controls. Of the seven miRNA of interest, three were observed in human blood, and of these, two (hsa-miR-144-3p and hsa-miR-1260a) appeared to be differentially expressed across the circulatory system. In particular, miRNA was at a higher concentration in hepatic effluent flow compared to other areas of circulation. Furthermore the proteins associated with these two miRNA play important roles in angiogenesis, supporting the hypothesis that miRNA originating from the liver may serve as protective agents against the development of PAVMs.