Why the study?
Cardiac hypertrophy is a major cause of heart failure, and RNA-binding proteins play diverse regulatory roles via alternative splicing in cardiovascular diseases.
RBMS1 drives cardiac hypertrophy via CTTN alternative splicing, identifying it as a novel therapeutic target for heart failure.
RBMS1 modulation may influence experimental hypertrophy; leaves open translation to human HF therapy.
Cardiac hypertrophy is one of the significant causes of heart failure and is closely related to the rising rate of hospitalization and readmissions. Given the diverse regulatory roles of alternative splicing in cardiovascular diseases, RNA-binding proteins have attracted increasing research attention. Here, for the first time, we discovered elevated expression of RBMS1 in heart tissues of patients with dilated cardiomyopathy and in mice with cardiac hypertrophy. We demonstrated that RBMS1 activated the PI3K/AKT signaling pathway by promoting the splicing CTTN to generate CTTN-Δe11 splicing isoform, resulting in cytoskeleton and sarcomere damage in cardiomyocytes. Additionally, pharmacological inhibition of RBMS1 by nortriptyline alleviated cardiac hypertrophy and heart failure. These results provide a new perspective for developing novel therapeutic approaches for cardiac hypertrophy and establish a theoretical basis for targeting RBMS1 in the clinical treatment of cardiac hypertrophy.
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Li et al. (2025) studied this question.
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