ESC Professional Members, Association Members (Ivory & above) benefit from year-round access to all the resources from their respective Association, and to all content from previous years. Fellows of the ESC (FESC), and professionals in training or under 40 years old, who subscribed to a Young Combined Membership package benefit from access to all ESC 365 content from all events, all editions, all year long. Find out more about ESC Memberships here.
MicroRNA-21 deteriorates left ventricular reverse remodeling by promoting cardiac fibrosis in non-ischemic cardiomyopathy
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)
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
,
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.
