PhD Candidate Western University Maple, Ontario, Canada
Disclosure(s): I do not have a relationship with a for-profit and/or a not-for-profit organization to disclose
Blinded Abstract: Introduction Endothelial dysfunction, central to the development of chronic diabetic complications, often manifests in the form of endothelial-to-mesenchymal transition (EndMT), where endothelial cells lose their endothelial properties and adopt mesenchymal-like phenotypes. miR-9 is a key regulator of glucose-induced EndMT in the retina and heart. however, the relation between high glucose and miR-9 suppression remain unclear. We hypothesized that despite playing a key role in EndMT in both organs, the regulatory linkage between high glucose and miR-9 inhibition differ between retina and heart.
Methodology The importance of miR-9 in EndMT was verified using our endothelial-specific miR-9 transgenic mice. Human cardiac and retinal endothelial cells were used to identify the differences in regulation of miR-9. siRNAs were used to elucidate the relation between miR-9 and potential regulators. Relevant genes were quantified via qPCR. Promoter methylation was also assessed via methylation-specific qPCR.
Results Glucose-induced EndMT caused dysfunction in the organs of diabetic wild type mice, but not in the miR-9 transgenic ones. ZFAS1, a long non-coding RNA which was found to regulate miR-9 expression in the heart, did not produce similar effects in retinal endothelial cells. Histone modification played an important role in glucose-induced miR-9 suppression in cardiac endothelial cells, while DNA methylation appears to be more important in retinal endothelial cells.
Discussion Endothelial cells can exhibit considerable heterogeneity across organs. Even though miR-9 is an important regulator of EndMT in both the heart and the retina, the way in which glucose influences miR-9 activity are different between the two organs.
