Ecklonia stolonifera Okamura Extract Suppresses Myocardial Infarction-Induced Left Ventricular Systolic Dysfunction by Inhibiting p300-HAT Activity.

Takahiro Katagiri,Tatsuya Morimoto,Satoshi Shimizu,Tatsuya Maekawa,Kiyoshi Mori,Koji Hasegawa,Kana Shimizu,Masafumi Funamoto,Philip Hawke,Hideo Hara,Maki Komiyama,Yoichi Sunagawa,Yasufumi Katanasaka

doi:10.3390/nu14030580

Takahiro Katagiri, Tatsuya Morimoto + Show 11 more

Open Access

https://doi.org/10.3390/nu14030580

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Abstract

Ecklonia stolonifera Okamura extract (ESE) has been reported to have various bioactive effects, but its effects on cardiovascular disease have not yet been investigated. First, primary neonatal rat cultured cardiomyocytes were treated with ESE and stimulated with phenylephrine (PE) for 48 h. ESE (1000 µg/mL) significantly suppressed PE-induced cardiomyocyte hypertrophy, hypertrophy-related gene transcription, and the acetylation of histone H3K9. An in vitro p300-HAT assay indicated that ESE directly inhibited p300-HAT activity. Next, one week after myocardial infarction (MI) surgery, rats (left ventricular fractional shortening (LVFS) < 40%) were randomly assigned to three groups: vehicle (saline, n = 9), ESE (0.3 g/kg, n = 10), or ESE (1 g/kg, n = 10). Daily oral administration was carried out for 8 weeks. After treatment, LVFS was significantly higher in the ESE (1 g/kg) group than in the vehicle group. The ESE treatments also significantly suppressed MI-induced increases in myocardial cell diameter, perivascular fibrosis, hypertrophy- and fibrosis-related gene transcription, and the acetylation of histone H3K9. These results suggest that ESE suppressed both hypertrophic responses in cardiomyocytes and the development of heart failure in rats by inhibiting p300-HAT activity. Thus, this dietary extract is a potential novel therapeutic strategy for heart failure in humans.

Highlights

Heart failure (HF) is a clinical syndrome caused by a structural and/or functional cardiac abnormality, resulting in reduced cardiac output and elevated intracardiac pressure at rest or during stress [1]
These results indicate that Ecklonia stolonifera Okamura extract (ESE) suppressed PE-induced hypertrophic responses in cardiomyocytes at least in part by inhibiting p300-histone acetyltransferase (HAT) activity
This study found that ESE suppressed both PE-induced cardiomyocyte hypertrophic response in primary cultured cardiomyocytes as well as cardiac hypertrophy and left ventricular systolic dysfunction in myocardial infarction (MI) rats

Summary

Introduction

Heart failure (HF) is a clinical syndrome caused by a structural and/or functional cardiac abnormality, resulting in reduced cardiac output and elevated intracardiac pressure at rest or during stress [1]. The incidence of HF increases with age, and the number of patients with HF is increasing rapidly along with the aging of the population [2], so addressing this problem is of great social and clinical importance. When the heart is stressed, the sympathetic nervous system and the renin-angiotensin system are activated, and these factors act on the heart to cause hypertrophy in individual cardiomyocytes [3,4] These factors bind to receptors on the cell surface and, through intracellular signaling pathways, eventually reach the cardiomyocyte nucleus. The histone acetyltransferase (HAT) activity of the transcriptional coactivator p300 is increased. This enhances the acetylation of the histone H3K9 and activates the transcription of hypertrophy-related genes [5,6,7]

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