View : 11 Download: 0

Discovery of shear-and side-specific mRNAs and miRNAs in human aortic valvular endothelial cells

Discovery of shear-and side-specific mRNAs and miRNAs in human aortic valvular endothelial cells
Holliday C.J.Ankeny R.F.Jo H.Nerem R.M.
Ewha Authors
Issue Date
Journal Title
American Journal of Physiology - Heart and Circulatory Physiology
0363-6135JCR Link
vol. 301, no. 3, pp. H856 - H867
The role of endothelial cells (ECs) in aortic valve (AV) disease remains relatively unknown; however, disease preferentially occurs in the fibrosa. We hypothesized oscillatory shear (OS) present on the fibrosa stimulates ECs to modify mRNAs and microRNAs (miRNAs) inducing disease. Our goal was to identify mRNAs and miRNAs differentially regulated by OS and laminar shear (LS) in human AVECs (HAVECs) from the fibrosa (fHAVECs) and ventricularis (vHAVECs). HAVECs expressed EC markers as well as some smooth muscle cell markers and functionally aligned with the flow. HAVECs were exposed to OS and LS for 24 h, and total RNA was analyzed by mRNA and miRNA microarrays. We found over 700 and 300 mRNAs down-and upregulated, respectively, by OS; however, there was no side dependency. mRNA microarray results were validated for 26 of 28 tested genes. Ingenuity Pathway Analysis revealed thrombospondin 1 (Thbs1) and NF-κB inhibitor-α (Nfkbia) as highly connected, shear-sensitive genes. miRNA array analysis yielded 30 shear-sensitive miRNAs and 3 side-specific miRNAs. miRNA validation confirmed 4 of 17 shear-sensitive miRNAs and 1 of 3 side-dependent miRNAs. Using miRWalk and several filtering steps, we identified shear-sensitive mRNAs potentially targeted by shear-sensitive miRNAs. These genes and signaling pathways could act as therapeutic targets of AV disease. © 2011 the American Physiological Society.
Appears in Collections:
일반대학원 > 바이오융합과학과 > Journal papers
Files in This Item:
There are no files associated with this item.
RIS (EndNote)
XLS (Excel)


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.