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PLoS One. 2014 May 1;9(5):e96577. doi: 10.1371/journal.pone.0096577. eCollection 2014.

The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes.

Author information

1
Department of Pediatrics (Cardiology), University of California San Diego, La Jolla, California, United States of America.
2
Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
3
Department of Cardiac Surgery, University Clinic of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
4
Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America; Computational Science Research Center & Biomedical Informatics Research Center San Diego State University, San Diego, California, United States of America.
5
Department of Pediatrics (Cardiology), University of California San Diego, La Jolla, California, United States of America; Rady Children's Hospital San Diego, San Diego, California, United States of America.

Erratum in

  • PLoS One. 2014;9(7):e104370.

Abstract

Aortic valve calcification is a significant and serious clinical problem for which there are no effective medical treatments. Individuals born with bicuspid aortic valves, 1-2% of the population, are at the highest risk of developing aortic valve calcification. Aortic valve calcification involves increased expression of calcification and inflammatory genes. Bicuspid aortic valve leaflets experience increased biomechanical strain as compared to normal tricuspid aortic valves. The molecular pathogenesis involved in the calcification of BAVs are not well understood, especially the molecular response to mechanical stretch. HOTAIR is a long non-coding RNA (lncRNA) that has been implicated with cancer but has not been studied in cardiac disease. We have found that HOTAIR levels are decreased in BAVs and in human aortic interstitial cells (AVICs) exposed to cyclic stretch. Reducing HOTAIR levels via siRNA in AVICs results in increased expression of calcification genes. Our data suggest that β-catenin is a stretch responsive signaling pathway that represses HOTAIR. This is the first report demonstrating that HOTAIR is mechanoresponsive and repressed by WNT β-catenin signaling. These findings provide novel evidence that HOTAIR is involved in aortic valve calcification.

PMID:
24788418
PMCID:
PMC4006892
DOI:
10.1371/journal.pone.0096577
[Indexed for MEDLINE]
Free PMC Article

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