Therapeutic inhibition of microRNA-34a ameliorates aortic valve calcification via modulation of Notch1-Runx2 signaling

Cardiovascular Research
Taku ToshimaMasafumi Watanabe

Abstract

Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease, and is increased with elderly population. However, effective drug therapy has not been established yet. This study aimed to investigate the role of microRNAs (miRs) in the development of CAVS. We measured the expression of 10 miRs which were reportedly involved in calcification by using human aortic valve tissue from patients who underwent aortic valve replacement with CAVS or aortic regurgitation (AR) and porcine aortic valve interstitial cells (AVICs) after treatment with osteogenic induction medium. We investigated whether a specific miR-inhibitor can suppress aortic valve calcification in wire injury CAVS mice model. Expression of miR-23a, miR-34a, miR-34c, miR-133a, miR-146a, and miR-155 was increased, and expression of miR-27a and miR-204 was decreased in valve tissues from CAVS compared with those from AR. Expression of Notch1 was decreased, and expression of Runt-related transcription factor 2 (Runx2) was increased in patients with CAVS compared with those with AR. We selected miR-34a among increased miRs in porcine AVICs after osteogenic treatment, which was consistent with results from patients with CAVS. MiR-34a increased calcium deposit...Continue Reading

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Citations

Oct 23, 2019·Cardiovascular Research·Michael A RaddatzW David Merryman
May 23, 2020·Journal of Cardiovascular Development and Disease·Neha AhujaDeborah Garrity
Dec 22, 2019·International Journal of Molecular Sciences·Rui SongXianzhong Meng
Oct 11, 2020·Biomolecules·Gloria GaroffoloMaurizio Pesce
Mar 21, 2020·Non-coding RNA Research·Joseph NaderValérie Metzinger-Le Meuth
Jul 10, 2021·Frontiers in Cardiovascular Medicine·Yidong WangBin Zhou
Oct 27, 2021·Cellular and Molecular Life Sciences : CMLS·Angela RaucciEstella Zuccolo

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