Yi-Xin-Shu capsule ameliorates cardiac hypertrophy by regulating RB/HDAC1/GATA4 signaling pathway based on proteomic and mass spectrometry image analysis.

Abstract

BACKGROUND:

Cardiac hypertrophy (CH) forms the main pathological basis of chronic heart failure (CHF). Mitigating and preventing CH is the key strategy for the treatment of ventricular remodeling in CHF. Yi-Xin-Shu capsule (YXS) has been commonly applied in the clinical treatment of CHF in Asian countries for several decades. However, the underlying mechanism of YXS has not been revealed yet.

PURPOSE:

To assess the efficiency of YXS in CH and identify its potential therapeutic targets for the managing of CH.

METHOD:

Ultrasonic cardiogram was used to evaluate the cardiac function of CH rats. Hematein Eosin (HE)-staining, Masson-staining and transmission electron microscope were used to measure the morphological changes, cardiac fibrosis degree and ultrastructure characteristics of cardiomyocytes, respectively. ELISA was used to detect the myocardial injury biomarkers. Then, the potential targets regulated by YXS were screened out via proteomic analysis and mass spectrometry image analysis. Finally, the targets were validated by real-time quantitative (RT-q) PCR, immunofluorescence, immunohistochemistry, and western-blotting methods.

RESULTS:

YXS improved the cardiac function of CH rats and attenuated the injuries in morphology and subcellular structure of cardiomyocytes. A core protein-protein interaction network was established on differentially expressed proteins (DEP) using proteomics analysis. GATA binding protein 4 (GATA4) was identified as the key target regulated by YXS. The results of mass spectrometry image analysis indicated that the expressions of histone deacetylase 1 (HDAC1) and retinoblastoma (RB) could also be regulated by YXS. Further valuative experiments showed that YXS may attenuate CH by regulating the RB/HDAC1/GATA4 signaling pathway.

CONCLUSIONS:

For the first time, this study discloses the precise mechanism investigation of the efficacy of YXS against CH. These data demonstrate that YXS may protect against CH by regulating the RB/HDAC1/GATA4 signaling pathway.

• Authors: Minyu Zhang, Feifei Guo, Xianyu Li, Minghua Xian, Tingting Wang, Hongwei Wu, Junying Wei, Ying Huang, Xiangning Cui, Sha Wu, Muxin Gong, Hongjun Yang
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 103 Pg. 154185 (Aug 2022) ISSN: 1618-095X [Electronic] Germany
• PMID: 35679794 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier GmbH.

Chemical References

• Drugs, Chinese Herbal
• GATA4 Transcription Factor
• Gata4 protein, rat
• yi-xin-shu
• Hdac1 protein, rat
• Histone Deacetylase 1

Topics

• Animals
• Cardiomegaly (drug therapy, metabolism)
• Drugs, Chinese Herbal
• GATA4 Transcription Factor (metabolism)
• Heart Failure (drug therapy, metabolism)
• Histone Deacetylase 1 (metabolism)
• Mass Spectrometry
• Myocytes, Cardiac (metabolism)
• Proteomics
• Rats
• Retinal Neoplasms (metabolism)
• Retinoblastoma (metabolism)
• Signal Transduction