Understanding the Functional Role of Shear- and Side-dependent MicroRNA-214 in Aortic Valve Biology

Authors

  • Swetha Rathan School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, USA.
  • Sivakkumar Arjunon The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University,, Atlanta, USA
  • Sandeep Kumar The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University,, Atlanta, USA
  • Joan Fernandez Esmerats The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University,, Atlanta, USA
  • Jack heath The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University,, Atlanta, USA
  • Md. Tausif Salim School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, USA
  • Robert Nerem Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, USA
  • Ajit Yoganathan School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, USA & The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University,, Atlanta, USA
  • Hanjoong Jo Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, USA

DOI:

https://doi.org/10.21542/gcsp.2025.hvbte.72

Abstract

Aortic valve (AV) disease is one of the leading causes of cardiovascular related deaths. It is a side-dependent pathology; preferentially occurring in the fibrosa of the AV. Altered shear stress induces inflammatory response in the fibrosa but not the ventricularis of AV. Studies showed that this preferential response could be in part due to differential gene expression in the fibrosa compared to the ventricularis. Based on our microarray analysis, four miRNAs (miRs-181a, 181b, 199a, and 214) were identified to be side-dependent in human AV endothelial cells. This study, using an ex vivo approach investigated if any of these microRNAs were involved in this side-dependent AV pathology. The fibrosa or ventricularis sides of freshly isolated porcine AV leaflets were exposed to either oscillatory shear stress (OS, +/-5dyne/cm2) or unidirectional pulsatile shear stress (LS, 80dyne/cm2). The leaflets were sheared in a shear stress bioreactor for 2 days in regular media and 3 & 7 days in osteogenic media. An increased thickness of the fibrosa layer, increase in miR-214 expression, and calcification was observed in the fibrosa exposed to OS compared to the ventricularis exposed to LS or OS. Using anti-miR-214, the miR-214 was silenced in fibrosa exposed to OS, to further understand its functional role in AV pathology. Silencing of miR-214 significantly increased the protein expression of TGFβ1, moderately increased collagen content but did not affect AV calcification. Thus miR-214 is a side- and shear-dependent miRNA that regulates mechanosensitive gene such as TGFβ1, a key cytokine involved in AV pathology.

Published

2025-10-06

Issue

Vol. 2025 No. HVBTE (2025): Proceedings of the The 10th Heart Valve Biology and Tissue Engineering Meeting

Section

Poster Presentations

License

Copyright (c) 2025 Swetha Rathan, Sivakkumar Arjunon, Sandeep Kumar, Joan Fernandez Esmerats, Jack heath, Md. Tausif Salim, Robert Nerem, Ajit Yoganathan, Hanjoong Jo

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

This is an open access article distributed under the terms of the Creative Commons Attribution license CC BY 4.0, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.