CYLD-mediated DNA damage coordinates pathological cardiac hypertrophy via RIPK1-dependent signaling

2026-05-01

PRE

Jiang, Xianyun

Shi, Mengyuan

Guo, Jiamin

Zhang, Jingjing

Li, Dingwei

Fan, Zujun

Ren, Fang-fang

Wu, Shu-jie

Zeng, Jingjing

Wu, Jian *

Li, Lei *

DOI：10.1016/j.yjmcc.2026.03.005

Original

Original request for help

Save

Abstract

En 中文

Cardiac remodeling under pressure overload involves maladaptive changes that lead to heart failure. This study investigated the role of the deubiquitinating enzyme CYLD in this process. We found that CYLD expression was significantly upregulated in hypertrophic mouse myocardium and cardiomyocytes. Silencing CYLD markedly attenuated pathological remodeling, improved cardiac function, and reduced DNA damage. Mechanistically, CYLD drives apoptosis by deubiquitinating RIPK1, a key signaling kinase. Inhibition of RIPK1 synergized with CYLD silencing to alleviate hypertrophy-associated DNA damage. Our findings establish the CYLD-RIPK1 axis as a critical regulator of the DNA damage response in cardiac hypertrophy and highlight CYLD inhibition as a promising therapeutic strategy for pressure overload-induced heart failure.

Keywords:

CYLD

DNA damage

RIPK1

Cardiac hypertrophy

Myocardial apoptosis

CYLD-mediated DNA damage coordinates pathological cardiac hypertrophy via RIPK1-dependent signaling

Abstract

Journal

Organization

Cited Papers

Citing Papers