The ADP-ribosyltransferases 3 (ART3) is a novel suppressor of pathological cardiac hypertrophy by ribosylating ITGA7.

Authors

Yilei Meng, Sangyu Hu, Fang Lin, Yuping Zhu, Yingying Xiong, Yizhuo Sun, Qin Lin, Mingxing Lu, Na Yi, Tao Xiao, Hanrui Wang, Jie Sheng, Ye Xu, Chenyu Li, Cuimei Zhao, Haojie Lu, Agapios Sachinidis, Li Li, Luying Peng

Published in

Acta pharmaceutica Sinica. B. Volume 16. Issue 9. Pages 5944-5960. Epub Jul 01, 2026.

Abstract

Pathological cardiac hypertrophy and heart failure remain mechanistically incompletely defined despite their clinical significance in cardiovascular disease. While ADP-ribosyltransferase cholera toxin-like (ARTC) enzymes modulate membrane protein function and downstream signaling via post-translational modifications, their role in cardiac pathology remains unexplored. Herein, we investigated the regulatory involvement of ADP-ribosyltransferase 3 (ART3) in myocardial remodeling. Cardiomyocyte-specific ART3 knockdown and overexpression murine models were established using adeno-associated virus serotype 9 (AAV9), with RNA-sequencing employed to profile ART3-dependent transcriptional responses in pathological cardiac hypertrophy. Functional validation was performed in complementary in vitro and in vivo hypertrophy models, complemented by immunoprecipitation-coupled mass spectrometry to identify ART3 substrates. ART3 was found to be cardiomyocyte-enriched and transcriptionally downregulated during progressive myocardial remodeling and heart failure. Cardiomyocyte-specific ART3 knockdown 3 accelerated the decompensatory transition of cardiac hypertrophy, whereas ART3 overexpression exerted significant anti-hypertrophic and anti-remodeling effects. Mechanistically, ART3 preserved cardiomyocyte mono-ADP-ribosyltransferase activity, catalyzing the site-specific mono-ADP-ribosylation (mADPr) of Integrin Subunit Alpha 7 (ITGA7) at residue R129. This post-translational modification was requisite for integrin signaling pathway activation, which mediated the observed cardioprotective effects. Collectively, these findings establish ART3 as a novel regulator of pathological cardiac hypertrophy by modulating ITGA7 via mADPr, highlighting its therapeutic potential as a target for heart failure intervention.

PMID:
42765066
Bibliographic data and abstract were imported from PubMed on 21 Sep 2026.

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