Publication: Data mining based on multiomic data integration to explore the mechanism by which a proprietary Chinese medicine improves cardiac hypertrophy in heart failure
Authors
Si-Jing Li ; Zi-Ru Li1 ; Xiao-Ming Dong ; Ao-Liu ; Hong-Yan Wu ; Quan-Fu Chen ; Wen-Jie Long ; Zhong-Qi Yang ; Zhi-Ling He ; Jin-Hua Kang
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Publisher
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Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-25-025
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info:eu-repo/semantics/article
Description
Abstract
Background. Heart failure remains a leading
cause of mortality worldwide with limited therapeutic
options. Xinyang Tablet (XYT), a clinically used
traditional Chinese medicine, demonstrates cardio
protective effects, but its mechanisms against cardiac
hypertrophy remain unclear. This study aimed to elucidate
the therapeutic mechanisms of XYT in heart failure with a
focus on oxidative stress and hypertrophy pathways.
Methods. Pressure-overload heart failure was
induced by transverse aortic constriction (TAC) in mice.
Cardiac function was assessed via histology
(hematoxylin-eosin [H&E], Masson's trichrome),
oxidative stress markers (dihydroethidium [DHE]
staining, superoxide dismutase [SOD]/malondialdehyde
[MDA]/glutathione peroxidase [GSH-Px] assays), and
molecular analyses. In vitro, angiotensin II (AngII)
treated HL-1 cardiomyocytes evaluated hypertrophy and
oxidative stress responses. Multiomic approaches,
including ultra-high performance liquid chromato
graphy-mass spectrometry (UHPLC-MS), network
pharmacology, RNA sequencing (RNA-seq), and single
cell RNA sequencing (scRNA-seq), identified XYT's bioactive compounds and hub targets, validated by AKT
inhibitor (MK-2206) experiments.
Results. XYT attenuated TAC-induced cardiac
hypertrophy and fibrosis, reducing heart volume,
cardiomyocyte cross-sectional area, and fibrotic markers
(collagen type I alpha 1 [COL1A1]/collagen type III alpha
1 [COL3A1]). XYT suppressed oxidative stress by
decreasing reactive oxygen species (ROS)/NADPH
oxidase 2 (NOX2)/NOX4 while increasing superoxide
dismutase 2 (SOD2)/GSH-Px in vivo and in vitro.
Bioinformatics identified 18 hub genes (e.g., histone
deacetylase 2 [HDAC2], SOD2) and enriched
phosphatidylinositol 3-kinase (PI3K)-protein kinase B
(AKT)/oxidative stress pathways. XYT inhibited
HDAC2/AKT/glycogen synthase kinase-3β (GSK-3β)
phosphorylation, while AKT inhibition with MK-2206
mimicked XYT's protective effects.
Conclusion. XYT ameliorates heart failure by
targeting HDAC2 to suppress AKT/GSK-3β signaling,
mitigating oxidative stress, cardiac hypertrophy, and
fibrosis, providing mechanistic evidence for clinical
translation.
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