Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with N G-nitro-L-arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2

Jin, Li; Lin, Ming Quan; Piao, Zhe; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Ryu, Yuhee; Sun, Simei; Kee, Hae Jin; Jeong, Myung Ho

doi:10.1097/hjh.0000000000001327

Cited by 55 publications

(37 citation statements)

References 40 publications

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“…Our results showed that long-term treatment with gallic acid reduced high blood pressure in spontaneously hypertensive rats (SHRs). This finding was consistent with our recent study, in which gallic acid lowered high blood pressure in a nitric oxide synthase inhibition-induced hypertension mouse model [17]. Hypertension usually accompanies left ventricular hypertrophy (LVH) [26].…”

Section: Discussionsupporting

confidence: 93%

Gallic acid attenuates calcium calmodulin‐dependent kinase II‐induced apoptosis in spontaneously hypertensive rats

Jin

Piao

Liu

et al. 2017

J Cellular Molecular Medi

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Hypertension causes cardiac hypertrophy and leads to heart failure. Apoptotic cells are common in hypertensive hearts. Ca2+/calmodulin‐dependent protein kinase II (CaMKII) is associated with apoptosis. We recently demonstrated that gallic acid reduces nitric oxide synthase inhibition‐induced hypertension. Gallic acid is a trihydroxybenzoic acid and has been shown to have beneficial effects, such as anti‐cancer, anti‐calcification and anti‐oxidant activity. The purpose of this study was to determine whether gallic acid regulates cardiac hypertrophy and apoptosis in essential hypertension. Gallic acid significantly lowered systolic and diastolic blood pressure in spontaneously hypertensive rats (SHRs). Wheat germ agglutinin (WGA) and H&E staining revealed that gallic acid reduced cardiac enlargement in SHRs. Gallic acid treatment decreased cardiac hypertrophy marker genes, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), in SHRs. The four isoforms, α, β, δ and γ, of CaMKII were increased in SHRs and were significantly reduced by gallic acid administration. Gallic acid reduced cleaved caspase‐3 protein as well as bax, p53 and p300 mRNA levels in SHRs. CaMKII δ overexpression induced bax and p53 expression, which was attenuated by gallic acid treatment in H9c2 cells. Gallic acid treatment reduced DNA fragmentation and the TUNEL positive cells induced by angiotensin II. Taken together, gallic acid could be a novel therapeutic for the treatment of hypertension through suppression of CaMKII δ‐induced apoptosis.

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Section: Discussionsupporting

confidence: 93%

Gallic acid attenuates calcium calmodulin‐dependent kinase II‐induced apoptosis in spontaneously hypertensive rats

Jin

Piao

Liu

et al. 2017

J Cellular Molecular Medi

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“…Studies have shown that HDACs are therapeutic targets for the treatment of several heart diseases including cardiac hypertrophy and fibrosis . Moreover, HDAC inhibitors have beneficial effects on pathological heart disease models, as these agents inhibit the increase in heart weight and cardiomyocyte size, restore ventricular remodeling, improve heart functions and reduce the expression of disease related genes and proteins .…”

Section: Discussionmentioning

confidence: 99%

Upregulation of C/EBPβ and TSC2 by an HDAC inhibitor CG200745 protects heart from DOCA‐induced hypertrophy

Lee

Kim

et al. 2018

Clin Exp Pharma Physio

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Histone deacetylases (HDACs) are a vast family divided into four major classes: class I (1, 2, 3, and 8), class II (4, 5, 6, 7, 9 and 10), class III (sirtuin family) and class IV (HDAC11). HDAC inhibition attenuates cardiac hypertrophy through suppression of the mechanistic target of rapamycin complex1 (mTORC1) signaling. HDAC inhibitors upregulate the expression of tuberous sclerosis complex 2 (TSC2), an mTORC1 inhibitor. However, the molecular mechanism underlying HDAC inhibitor-mediated upregulation of TSC2 is unclear. We hypothesized that an HDAC inhibitor, CG200745 (CG), ameliorates cardiac hypertrophy through the inhibition of mTORC1 signaling by upregulating of the CCAAT/enhancer-binding protein-β (C/EBP-β)/TSC2 pathway. To establish a cardiac hypertrophy model, deoxycorticosterone acetate (DOCA, 40 mg/kg/wk) was subcutaneously injected for 4 weeks into Sprague-Dawley rats. All rats were unilaterally nephrectomized and had free access to drinking water containing 1% NaCl with or without CG of different concentrations. The expression level of TSC2 and C/EBP-β was measured by quantitative real-time PCR (qRT-PCR) and western blot analysis. Acetylation of C/EBP-β was analyzed by immunoprecipitation. The recruitment of C/EBP-β and polymerase II (Pol II) on TSC2 promoter region was analyzed by chromatin immunoprecipitation (ChIP). CG treatment increased the expression of TSC2. In addition, CG treated rats showed an increased in the expression and acetylation of C/EBP-β, owing to the increase in the recruitment of C/EBP-β and Pol II at Tsc2 gene promoter. Thus, CG ameliorates cardiac hypertrophy through the inhibition of mTORC1 signaling via upregulation of the C/EBP-β/TSC2 pathway in DOCA-induced hypertensive rats.

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“…To measure cardiac fibrosis, we performed Masson's trichrome staining as described previously, with some modifications . Briefly, heart sections were incubated with prewarmed Bouin's solution for 30 minutes to intensify the final coloration.…”

Section: Methodsmentioning

confidence: 99%

“…To measure cardiac fibrosis, we performed Masson's trichrome staining as described previously, with some modifications. 21 Briefly, heart sections were incubated with prewarmed Bouin's solution for 30 minutes to intensify the final coloration. Nuclei were stained by exposure to Weigert's haematoxylin for 20 minutes, and cytoplasm and muscle were stained by incubation with Biebrich scarlet-acid fuchsin solution for 20 minutes.…”

Section: Histology and Masson's Trichrome Stainingmentioning

confidence: 99%

Gentisic acid attenuates pressure overload‐induced cardiac hypertrophy and fibrosis in mice through inhibition of the ERK1/2 pathway

Sun

Kee

Jin

et al. 2018

J Cellular Molecular Medi

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We previously reported that gentisic acid (2,5‐dihydroxybenzoic acid) is the third most abundant phenolic component of Dendropanax morbifera branch extracts. Here, we investigated its effects on cardiac hypertrophy and fibrosis in a mouse model of pressure overload and compared them to those of the beta blocker bisoprolol and calcium channel blocker diltiazem. Cardiac hypertrophy was induced in mice by transverse aortic constriction (TAC). Beginning 2 weeks after this procedure, the mice were given daily intraperitoneal injections of gentisic acid (100 mg/kg/d), bisoprolol (5 mg/kg/d) or diltiazem (10 mg/kg/d) for 3 weeks. Cardiac hypertrophy was evaluated by the heart weight‐to‐body weight ratio, the cardiomyocyte cross‐sectional area after haematoxylin and eosin staining, and echocardiography. Markers of cardiac hypertrophy and fibrosis were tested by reverse transcription‐quantitative real‐time polymerase chain reaction, western blotting and Masson's trichrome staining. The suppressive effects of gentisic acid treatment on TAC‐induced cardiac hypertrophy and fibrosis were comparable to those of bisoprolol administration. Cardiac hypertrophy was reversed and left ventricular septum and posterior wall thickness were restored by gentisic acid, bisoprolol and diltiazem treatment. Cardiac hypertrophic marker gene expression and atrial and brain natriuretic peptide levels were decreased by gentisic acid and bisoprolol, as were cardiac (interstitial and perivascular) fibrosis and fibrosis‐related gene expression. Cardiac hypertrophy‐associated upregulation of the transcription factors GATA4 and Sp1 and activation of extracellular signal‐regulated kinase 1/2 were also negated by these drugs. These results suggest that gentisic acid could serve as a therapeutic agent for cardiac hypertrophy and fibrosis.

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Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with N G-nitro-L-arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2

Abstract: These results suggested that gallic acid may be a potential therapeutic agent for the treatment of cardiovascular diseases with hypertension and cardiac fibrosis.

Cited by 55 publications

References 40 publications

Gallic acid attenuates calcium calmodulin‐dependent kinase II‐induced apoptosis in spontaneously hypertensive rats

Gallic acid attenuates calcium calmodulin‐dependent kinase II‐induced apoptosis in spontaneously hypertensive rats

Upregulation of C/EBPβ and TSC2 by an HDAC inhibitor CG200745 protects heart from DOCA‐induced hypertrophy

Gentisic acid attenuates pressure overload‐induced cardiac hypertrophy and fibrosis in mice through inhibition of the ERK1/2 pathway

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