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MicroRNA-21 deteriorates left ventricular reverse remodeling by promoting cardiac fibrosis in non-ischemic cardiomyopathy

Session Poster Session 2

Speaker Ken Watanabe

Event : ESC Congress 2019

  • Topic : basic science
  • Sub-topic : Genetics, Epigenetics, ncRNA
  • Session type : Poster Session

Authors : K Watanabe (Yamagata,JP), T Narumi (Yamagata,JP), T Watanabe (Yamagata,JP), T Aono (Yamagata,JP), J Goto (Yamagata,JP), T Sugai (Yamagata,JP), T Toshima (Yamagata,JP), S Kato (Yamagata,JP), H Tamura (Yamagata,JP), S Nishiyama (Yamagata,JP), H Takahashi (Yamagata,JP), T Arimoto (Yamagata,JP), T Shishido (Yamagata,JP), M Watanabe (Yamagata,JP)

Authors:
K. Watanabe1 , T. Narumi1 , T. Watanabe1 , T. Aono1 , J. Goto1 , T. Sugai1 , T. Toshima1 , S. Kato1 , H. Tamura1 , S. Nishiyama1 , H. Takahashi1 , T. Arimoto1 , T. Shishido1 , M. Watanabe1 , 1Yamagata University, Department of Cardiology, Pulmonology, and Nephrology - Yamagata - Japan ,

Topic(s):
Basic Science - Cardiac Biology and Physiology: Genetics, Epigenetics, ncRNA

Citation:
European Heart Journal ( 2019 ) 40 ( Supplement ), 928

Background: Left ventricular reverse remodeling (LVRR) contributes to better outcomes in patients with non-ischemic cardiomyopathy (NICM). It is reported that LVRR is associated with progression of cardiac fibrosis. MicroRNAs (miRs) have emerged as powerful regulators of post-transcriptional gene expression. We focused on miR-21, which plays a key role in pathogenesis of fibrosis in multiple organs. The aim of this study was to clarify the effect of miR-21 on cardiac fibrosis and LVRR in patients with NICM.

Methods: We measured plasma miR-21 levels in 16 patients with NICM. LVRR was defined as increased LVEF by ≥10% and decreased LV end-diastolic diameter index by ≥10% from baseline data after optimal medication treatment at 1-year of follow-up. Further, we examined miR-21 expression and its potential role in cardiac fibrosis induced by transverse aortic constriction (TAC) in mice and angiotensin II (Ang II) stimulation in neonatal rat cardiomyocytes (NRCMs).

Results: There were 12 patients without LVRR and 4 patients with LVRR. Plasma miR-21 levels were significantly higher in patients without LVRR compared with those with LVRR. In TAC mice heart, miR-21 levels were significantly increased and programmed cell death 4 (PDCD4), a main target of miR-21, was decreased. In vitro, miR-21 levels were significantly increased and its upstream transcriptional factor, activator protein 1 (AP-1), was activated by Ang II stimulation in NRCMs. After transfection of miR-21 specific inhibitor, PDCD4 levels were upregulated. Furthermore, AP-1 activity, expression of collagen type I, and α-smooth muscle actin levels were significantly decreased after miR-21 inhibition.

Conclusions: These findings suggested that miR-21/PDCD4/AP-1 feedback loop pathway was involved in LVRR in patients with NICM by promoting cardiac fibrosis. MiR-21 can be the therapeutic target in NICM.

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