Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling

Gitau, Samuel Chege; Li, Xuelian; Zhao, Dandan; Guo, Zhenfeng; Liang, Haihai; Qian, Ming; Lv, Le; Li, Tianshi; Xu, Bin; Wang, Zhiguo; Zhang, Yong; Xu, Chaoqian; Lu, Yanjie; Du, Zhiming; Shan, Hongli; Yang, Baofeng

doi:10.1007/s11684-015-0421-z

Cited by 19 publications

(21 citation statements)

References 50 publications

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“…In our previous study, we confirmed that aspirin attenuates cardiac hypertrophy and alleviates cardiac remodelling [6]. This study demonstrated that aspirin reduced cardiac interstitial fibrosis in transverse aortic constriction (TAC) mice.…”

Section: Resultssupporting

confidence: 67%

“…In our previous study, aspirin was shown to possess significant anti-hypertrophic properties and to down-regulate β-catenin/Akt signalling that had been induced by left ventricular pressure overload in mice [6]. In addition to ventricular hypertrophy, pressure overload results in cardiac remodelling, reactive fibrosis, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Aspirin attenuates Ang II-induced inflammation via the inhibition of Erk1/2 and NF-κB activation in bone marrow mesenchymal stem cells [36]. Our previous study showed that at clinically relevant doses for anti-thrombotic therapy, aspirin possesses significant anti-hypertrophic properties and causes the down-regulation of β-catenin and p-Akt, which may be part of the signalling mechanism necessary for these effects [6]. In the present study, the dosage of aspirin used coincided with the guidelines of the American College of Chest Physicians (ACCP) [37], the American College of Cardiology/American Heart Association, and the European Society of Cardiology [38].…”

Section: Discussionmentioning

confidence: 99%

“…Cardiac hypertrophy was induced by TAC in C57BL/6 mice (20-22 g), as described previously [5]. Briefly, the mice were anesthetized using phenobarbital (50 mg·kg -1 , intraperitoneally) and were subjected to either TAC or a sham control operation [6]. The TAC procedure consisted of a 7.0 nylon suture being placed around the transverse aorta between the innominate and left carotid arteries.…”

Section: Methodsmentioning

confidence: 99%

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Aspirin Reduces Cardiac Interstitial Fibrosis by Inhibiting Erk1/2-Serpine2 and P-Akt Signalling Pathways

Wang²,

Qili

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cardiac interstitial fibrosis is an abnormality of various cardiovascular diseases, including myocardial infarction, hypertrophy, and atrial fibrillation, and it can ultimately lead to heart failure. However, there is a lack of practical therapeutic approaches to treat fibrosis and reverse the damage to the heart. The purpose of this study was to investigate the effect of long-term aspirin administration on pressure overload–induced cardiac fibrosis in mice and reveal the underlying mechanisms of aspirin treatment. Methods: C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 10 mg·kg^-1·day^-1 of aspirin for 4 weeks. Masson staining and a collagen content assay were used to detect the effects of aspirin on cardiac fibrosis in vivo and in vitro. Western blot and qRT-PCR were applied to examine the impact of aspirin on extracellular signal-regulated kinases (Erks), p-Akt/β-catenin, SerpinE2, collagen I, and collagen III levels in the mice heart. Results: Aspirin significantly suppressed the expression of α-smooth muscle actin (α-SMA; 1.19±0.19-fold) and collagen I (0.95±0.09-fold) in TAC mice. Aspirin, at doses of 100 and 1000 µM, also significantly suppressed angiotensin II-induced α-SMA and collagen I in cultured CFs. The enhanced phosphorylation of Erk1/2 caused by TAC (p-Erk1, 1.49±0.19-fold; p-Erk2, 1.96±0.68-fold) was suppressed by aspirin (p-Erk1, 1.04±0.15-fold; p-Erk2, 0.87±0.06-fold). SerpinE2 levels were suppressed via the Erk1/2 signalling pathway following treatment with aspirin (1.36±0.12-fold for TAC; 1.06±0.07-fold for aspirin+TAC). The p-Akt and β-catenin levels were also significantly inhibited in vivo and in vitro. Conclusions: Our study reveals a novel mechanism by which aspirin alleviates pressure overload-induced cardiac interstitial fibrosis in TAC mice by suppressing the p-Erk1/2 and p-Akt/β-catenin signalling pathways.

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Section: Resultssupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Aspirin Reduces Cardiac Interstitial Fibrosis by Inhibiting Erk1/2-Serpine2 and P-Akt Signalling Pathways

Wang²,

Qili

et al. 2018

Cell Physiol Biochem

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“…The CMs were fixed with 2.5% glutaraldehyde (pH 7.4) at 4°C overnight, and subsequently fixed in 1.0% osmium tetroxide for 1 h. The monolayer was blocked in uranyl acetate as previously described [19], and observed under an electron microscope (JEM-1220, JEOL, Ltd., Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

Cardiomyocyte Derived miR-328 Promotes Cardiac Fibrosis by Paracrinely Regulating Adjacent Fibroblasts

Zhao¹,

Cui²,

He³

et al. 2018

Cell Physiol Biochem

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Background/Aims: In our previous study, we demonstrated that elevated expression of miR-328 is a potent determinant of cardiac fibrosis during myocardial infarction (MI). In the present study, histological examination revealed progressive fibrosis in transgenic mice overexpressing cardiomyocyte-specific miR-328. This study investigated whether the transfer of miR-328 from cardiomyocytes (CMs) to cardiac fibroblasts (CFs) in a paracrine manner contributes to myocardial fibrosis. Methods: Myocardial infarction was established by the occlusion of the left coronary artery. Masson’s trichrome staining and collagen assays were used to evaluate the progression of fibrosis. The vesicles and translocation of miR-328 in a co-culture assay system were respectively observed using transmission electron microscopy (TEM) and immunofluorescence staining (IF). Real-time PCR was employed to detect the level of miR-328, Col1α1 and Col3α1. The protein expression of Col1α1, TGF-βRIII, p-smad2/3 (phosphorylated-smad2/3) and TGF-β1 were probed using western blot analysis. Results: Cardiomyocyte-specific miR-328 overexpressing transgenic (TG) mice showed enhanced collagen deposition and provoked cardiac fibrosis by the activation of the TGF-β1 pathway, and this effect was abrogated after knockdown of endogenous miR-328 in mice. Correspondingly, the expression of miR-328 was increased in CFs co-cultured with CMs transfected with miR-328 mimics, likely in a paracrine manner. The cardiomyocyte-mediated augmentation of miR-328 contributes to fibrogenesis in CFs, and this pro-fibrotic effect was reversed after the transfection of miR-328 inhibitor in CFs. Conclusion: A novel molecular mechanism for miR-328 derived from CMs as a paracrine signaling mediator of cardiac fibrogenesis further demonstrates that miR-328 is a potential therapeutic target.

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Infliximab substantially re‐silenced Wnt/β‐catenin signaling and ameliorated doxorubicin‐induced cardiomyopathy in rats

Mohamed

Askar

Shaheen

et al. 2023

J Biochem & Molecular Tox

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The release of inflammatory cytokines, namely tumor necrosis factor-α (TNF-α), plays an important role in the pathogenesis of cardiomyopathy. TNF-α increases in plasma and in myocardium of heart failure patients. We aimed to investigate the role of TNF-α inhibitor (infliximab; IFX) in regulating dilated cardiomyopathy (DCM) induced in rats. DCM was induced in rats by doxorubicin (DOX; 3.5 mg. kg −1 , i.p) twice weekly for 3 weeks (21 mg. kg −1 cumulative dose). DCM rats were treated with RPL (1 mg. kg −1 orally, daily), IFX (5 mg. kg −1 ; i.p. once) or their combination for 4 weeks starting next day of last DOX dose. Echocardiography was conducted followed by a collection of blood and left ventricle (LV) for biochemical and histological investigations. DCM rats revealed deteriorated cardiac function (increased CK-MB activity, LVIDs, LVIDd, ESV, and EDV, while decreased EF% and FS%), hypertrophy (increased HW/TL, β-MHC, and α-actin), inflammation (increased IL-1β, IL-6, and TNF-α). The activation of Wnt/β-catenin along with increased gene expression of RAS components (RENIN, ACE, and AT1) were evident.LV architecture also revealed abnormalities and some degree of fibrosis. Treatment with RPL and/or IFX suppressed TNF-α and consequently improved most of these parameters suppressing Wnt/β-catenin/RAS axis. Combined RPL and IFX treatment was the best among all treatments. In conclusion, Wnt/β-catenin/RAS axis is implicated in DOX-induced cardiomyopathy. The upstream TNF-α was proved for the first time in-vivo to stimulate this axis where its inhibition by RPL or IFX prevented DCM. Targeting this axis at two points using RPL and IFX showed better therapeutic efficacy.

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Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling

Cited by 19 publications

References 50 publications

Aspirin Reduces Cardiac Interstitial Fibrosis by Inhibiting Erk1/2-Serpine2 and P-Akt Signalling Pathways

Aspirin Reduces Cardiac Interstitial Fibrosis by Inhibiting Erk1/2-Serpine2 and P-Akt Signalling Pathways

Cardiomyocyte Derived miR-328 Promotes Cardiac Fibrosis by Paracrinely Regulating Adjacent Fibroblasts

Infliximab substantially re‐silenced Wnt/β‐catenin signaling and ameliorated doxorubicin‐induced cardiomyopathy in rats

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