Arq. Bras. Cardiol. 2024; 121(10): e20240181

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

Xiaojun Zhang, Zhen Chen, Ning Zhang, Bo Yu, Wei Li, Mengli Zhang, Xian Wu, Ganzhe Liu, Meizhen Dong

DOI: 10.36660/abc.20240181i

This Original Article is referred by the Short Editorial "Long Non-Coding RNA CCAT2 and Pathological Cardiac Remodeling".

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.