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

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

Author information

1
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. fiedler.jan@mh-hannover.de.
2
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
3
Integrated Research and Treatment Center Transplantation, Hannover Medical School, Hannover, Germany.
4
Department of Nephrology, Hannover Medical School, Hannover, Germany.
5
Department of Cardiology, Klinikum Vest, Recklinghausen, Germany.
6
Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany.
7
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. thum.thomas@mh-hannover.de.
8
Integrated Research and Treatment Center Transplantation, Hannover Medical School, Hannover, Germany. thum.thomas@mh-hannover.de.
9
National Heart and Lung Institute, Imperial College London, London, UK. thum.thomas@mh-hannover.de.
10
REBIRTH Excellence Cluster, Hannover Medical School, Hannover, Germany. thum.thomas@mh-hannover.de.

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

PMID:
30840186
DOI:
10.1007/s12265-019-09880-7

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