LncRNA CCAT2 Knockdown Alleviates Pressure Overload or Ang II-Induced Cardiac Hypertrophy Via Disruption of the Wnt/β-Catenin Signaling

  • Arq Bras Cardiol. 2024 Oct;121(10):e20240181. doi: 10.36660/abc.20240181.
Xiaojun Zhang  1 ,  Zhen Chen  2 ,  Ning Zhang  1 ,  Bo Yu  2 ,  Wei Li  2 ,  Mengli Zhang  2 ,  Xian Wu  2 ,  Ganzhe Liu  2 ,  Meizhen Dong  1
Affiliations
  • 1. Department of Emergency, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shangdong University, Qingdao, Shangdong - China.
  • 2. The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei - China.
PMID: 39536197 DOI: 10.36660/abc.20240181
Abstract

Background: Sustained pathological cardiac hypertrophy (CH) is an independent risk factor for increased incidence and mortality of cardiovascular events.

Objectives: This research was designed to unravel the role of long non-coding RNA (LncRNA) CCAT2 in CH progression.

Methods: Transverse aortic constriction (TAC) procedures were conducted to construct a pressure overload-induced in vivo CH model. Angiotensin II (Ang II) treatment was utilized to induce hypertrophic rat cardiomyocyte H9c2 cells.

Results: In vivo results showed that silencing of CCAT2 reduced cardiomyocyte surface area, alleviated cardiac fibrosis, and decreased β-MHC, ANP, and BNP levels in CH mouse models. In vitro results revealed that CCAT2 knockdown reduced cell surface area and attenuated β-MHC, ANP, and BNP levels in hypertrophic H9c2 cells. Besides, CCAT2 silencing decreased the levels of active β-catenin, phosphorylated-GSK-3β, and Wnt target genes (c-Myc, cyclinD1, and c-Jun) in CH mice and hypertrophic H9c2 cells. Importantly, treatment with the Wnt/β-catenin pathway activator LiCl reversed the suppression of CCAT2 knockdown on H9c2 cell surface area and MHC, ANP, and BNP levels.

Conclusions: Collectively, CCAT2 silencing plays a protective role against CH through inactivating the Wnt/β-catenin signaling, which suggests that CCAT2 might become a promising therapeutic target for CH.

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