Dataset Information

HFpEF model heart failure mouse treated with traditional herbal medicine Goreisan

ABSTRACT: In this project we aimed to investigate the effect of Goreisan (GRS, traditional herbal medicine) on HFpEF model heart failure mouse. HFpEF was induced by administration of high-fat diet (HFD)and N-nitro-L-arginine methyl ester (L-NAME), with or without GRS. Mouse heart proteome was analyzed with LC/MS/MS.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Masashi Hiramoto

PROVIDER: PXD049259 | JPOST Repository | Tue Sep 02 00:00:00 GMT+01:00 2025

REPOSITORIES: jPOST

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Publications

Goreisan attenuates cardiac hypertrophy and diastolic dysfunction in heart failure with preserved ejection fraction induced by HFD/L-NAME via regulation of ICAT-β-catenin/ERK axis.

Isayama Yoko Shojima YS Matsushima Shouji S Shinohara Keisuke K Isayama Koichi K Enzan Nobuyuki N Yamamoto Taishi T Sada Masashi M Miyake Ryo R Tsutsui Yoshitomo Y Toyohara Takayuki T Nishimura Ryohei R Ikeda Yuki Y Noda Eri E Otsuru Wataru W Tokumoto Shuya S Watanabe Masatsugu M Ikeda Masataka M Hashimoto Toru T Kinugawa Shintaro S Tsutsui Hiroyuki H Abe Kohtaro K

Hypertension research : official journal of the Japanese Society of Hypertension 20250903 11

Heart failure with preserved ejection fraction (HFpEF), characterized by cardiac hypertrophy and diastolic dysfunction, is increasing worldwide. Goreisan (GRS) is a traditional herbal formulation; its component attenuates cardiomyocyte hypertrophy. This study aimed to investigate the effect of GRS on the pathophysiology of HFpEF. Administration of a high fat diet (HFD, 60% fat) and N-nitro-L-arginine methylester (L-NAME, 0.5 g/L in drinking water) increased heart and lung weights in C57BL/6 mice ...[more]

PMID: 40903537

Similar Datasets

Project description:<p>Increased protein acetylation is frequently observed in the failing heart, including in hearts with heart failure with preserved ejection fraction (HFpEF). However, the role of protein acetylation in cardiac metabolic impairments during the pathogenesis of HFpEF remains insufficiently investigated. In this study, a two-hit strategy, involving a high-fat diet and Nω-nitro-L-arginine methyl ester (L-NAME), was employed to induce the HFpEF model in mice. Significant cardiac diastolic dysfunction, pathological remodeling, and enhanced protein hyperacetylation were observed in the hearts of the two-hit HFpEF mice. Acetylome profiling revealed that the hyperacetylated proteins were predominantly localized to mitochondria and enriched in metabolic pathways, particularly in fatty acid oxidation (FAO). Furthermore, the HFpEF heart exhibited reduced FAO capacity and abnormal lipid accumulation. Activation of mitochondrial protein deacetylation restored FAO capacity and alleviated cardiac dysfunction in the HFpEF heart, whereas inhibition of mitochondrial deacetylase directly induced lipid metabolism disorders in cardiomyocytes. Notably, we identified Dlat, a pyruvate metabolism enzyme, as the key transacetylase responsible for mitochondrial protein hyperacetylation in the HFpEF heart. Overexpression of Dlat enhanced FAO-related protein acetylation and exacerbated cardiac lipid metabolism disturbances, thereby inducing pathological changes resembling the HFpEF phenotype. In contrast, Dlat knockdown effectively mitigated FAO inhibition and functional impairment in the two-hit HFpEF mice. Through discovery-driven approaches, we demonstrated that Dlat directly binds to the alpha subunit of mitochondrial trifunctional protein (HADHA) and triggers its acetylation at the K728 site, thereby inactivating HADHA enzymatic activity. Reactivating HADHA, either by cardiac-specific HADHA overexpression or oral administration of a biogenic polyamine, restored cardiac FAO capacity and prevented the development of HFpEF. Our study provides a mechanistic basis linking protein hyperacetylation, FAO inhibition, and the development of HFpEF. Activation of mitochondrial deacetylase or enhancement of cardiac FAO capacity may offer novel strategies for restoring cardiac metabolic homeostasis and function in HFpEF.</p>

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