Identification of miR-143 as a Major Contributor for Human Stenotic Aortic Valve Disease

J Cardiovasc Transl Res. 2019 Oct;12(5):447-458. doi: 10.1007/s12265-019-09880-7. Epub 2019 Mar 6.

Abstract

Calcification of aortic valves leads to aortic stenosis mainly in elderly individuals, but the underlying molecular mechanisms are still not understood. Here, we studied microRNA (miR, miRNA) expression and function in healthy and stenotic human aortic valves. We identified miR-21, miR-24, and miR-143 to be highly upregulated in stenotic aortic valves. Using luciferase reporter systems, we found direct binding of miR-143 to the 3'UTR region of the matrix gla protein (MGP), which in turn is a key factor to sustain homeostasis in aortic valves. In subsequent experiments, we demonstrated a therapeutic potential of miRNA regulation during calcification in cardiac valvular interstitial cells. Collectively, our data provide evidence that deregulated miR expression contributes to the development of stenotic valve disease and thus form novel therapeutic opportunities of this severe cardiovascular disease.

Keywords: Calcium deposition dependent on miR-143; Human aortic stenosis; miR signature in aortic stenosis; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Aged
  • Aged, 80 and over
  • Animals
  • Aortic Valve / metabolism*
  • Aortic Valve / pathology*
  • Aortic Valve Stenosis / genetics
  • Aortic Valve Stenosis / metabolism*
  • Aortic Valve Stenosis / pathology
  • Binding Sites
  • Calcinosis / genetics
  • Calcinosis / metabolism*
  • Calcinosis / pathology
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Case-Control Studies
  • Cells, Cultured
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Osteogenesis
  • Signal Transduction
  • Sus scrofa
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • MIRN143 microRNA, human
  • MicroRNAs
  • matrix Gla protein

Supplementary concepts

  • Aortic Valve, Calcification of