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PLoS One. 2020 Feb 10;15(2):e0226053. doi: 10.1371/journal.pone.0226053. eCollection 2020.

The association between microRNA-21 and hypertension-induced cardiac remodeling.

Author information

1
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
2
Department of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine, Hamamatsu, Japan.
3
Department of Advanced Cardiovascular Therapeutics, Yamagata University School of Medicine, Yamagata, Japan.
4
Department of Advanced Heart Rhythm Therapeutics, Yamagata University School of Medicine, Yamagata, Japan.

Abstract

Hypertension is a major public health problem among the aging population worldwide. It causes cardiac remodeling, including hypertrophy and interstitial fibrosis, which leads to development of hypertensive heart disease (HHD). Although microRNA-21 (miR-21) is associated with fibrogenesis in multiple organs, its contribution to cardiac remodeling in hypertension is poorly understood. Circulating miR-21 level was higher in patients with HHD than that in the control subjects. It also positively correlated with serum myocardial fibrotic markers. MiR-21 expression levels were significantly upregulated in the mice hearts after angiotensin II (Ang II) infusion or transverse aortic constriction (TAC) compared with control mice. Expression level of programmed cell death 4 (PDCD4), a main target of miR-21, was significantly decreased in Ang II infused mice and TAC mice compared with control mice. Expression levels of transcriptional activator protein 1 (AP-1) and transforming growth factor-β1 (TGF-β1), which were downstream targets of PDCD4, were increased in Ang II infused mice and TAC mice compared with control mice. In vitro, mirVana-miR-21-specific inhibitor attenuated Ang II-induced PDCD4 downregulation and contributed to subsequent deactivation of AP-1/TGF-β1 signaling pathway in neonatal rat cardiomyocytes. Thus, suppression of miR-21 prevents hypertrophic stimulation-induced cardiac remodeling by regulating PDCD4, AP-1, and TGF-β1 signaling pathway.

PMID:
32040481
DOI:
10.1371/journal.pone.0226053
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