Mechanisms contributing to cardiac remodelling

Wu, Qin; Yang, Xiao; Yuan, Yuan; Ma, Zhen‐Guo; Liao, Hai‐Han; Liu, Chen; Zhu, Jinxiu; Zheng, Yang; Deng, Wei; Tang, Qi‐Zhu

doi:10.1042/cs20171167

Cited by 167 publications

(124 citation statements)

References 258 publications

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“…P38 inhibitors (SB203580 or SB202190) suppressed hypertrophic stimuli induced myocyte growth and dominant negative P38 delivered by adenoviruses ( Zechner et al, 1997 ; Liang and Molkentin, 2003 ). Our previous studies have reported that many molecular and plant extracts ameliorate pressure overload-induced cardiac hypertrophy via MAPKs inhibition ( Wu et al, 2017b ). ATF3 exerts negative feedback on the ERK and JNK pathways to modulate cardiac remodeling ( Zhou et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Andrographolide Protects against Aortic Banding-Induced Experimental Cardiac Hypertrophy by Inhibiting MAPKs Signaling

Ni²,

Zhang³

et al. 2017

Front. Pharmacol.

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Despite therapeutic advances, heart failure-related mortality rates remain high. Therefore, understanding the pathophysiological mechanisms involved in the remodeling process is crucial for the development of new therapeutic strategies. Andrographolide (Andr), a botanical compound, has potent cardio-protective effects due to its ability to inhibit mitogen-activated protein kinases (MAPKs). Andr has also been shown to inhibit inflammation and apoptosis, which are factors related to cardiac hypertrophy. Our aim was to evaluate the effects of Andr on cardiac hypertrophy and MAPKs activation. Thus, mice were subjected to aortic banding (AB) with/without Andr administration (25 mg/kg/day, orally). Cardiac function was accessed by echocardiography and hemodynamic parameters. Our results showed that Andr administration for 7 weeks decreased cardiac dysfunction and attenuated cardiac hypertrophy and fibrosis in AB mice. Andr treatment induced a strong reduction in the transcription of both hypertrophy (ANP, BNP, and β-MHC) and fibrosis related genes (collagen I, collagen III, CTGF, and TGFβ). In addition, cardiomyocytes treated with Andr showed a reduced hypertrophic response to angiotensin II. Andr significantly inhibited MAPKs activation in both mouse hearts and cardiomyocytes. Treatment with a combination of MAPKs activators abolished the protective effects of Andr in cardiomyocytes. Furthermore, we found that Andr also inhibited the activation of cardiac fibroblasts via the MAPKs pathway, which was confirmed by the application of MAPKs inhibitors. In conclusion, Andr was found to confer a protective effect against experimental cardiac hypertrophy in mice, suggesting its potential as a novel therapeutic drug for pathological cardiac hypertrophy.

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Section: Discussionmentioning

confidence: 99%

Andrographolide Protects against Aortic Banding-Induced Experimental Cardiac Hypertrophy by Inhibiting MAPKs Signaling

Ni²,

Zhang³

et al. 2017

Front. Pharmacol.

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“…Cardiac remodelling involves myocyte hypertrophy, apoptosis and extracellular matrix accumulation. 2,29 We first observed the effects of Flt3 activation with the specific ligand FL on the function and morphology of maladaptive heart induced by continuous infusion of Ang II in mice. Echocardiographic analysis revealed that Ang II induced significant decreases in left ventricular ejection fraction (LVEF%), left ventricular fractional shortening (LVFS%) and left ventricular posterior wall thickness at end-diastole (LVPWd), but increases in left ventricular internal dimension at end-diastole (LVIDd).…”

Section: Flt3 Activation Improves Ang Iiinduced Cardiac Dysfunctionmentioning

confidence: 99%

“…Maladaptive cardiac remodelling is a chronic process in response to various pathologic stresses or diseases, which is intimately associated with the progression of heart failure (HF). [1][2][3] The hallmarks of adverse cardiac remodelling include progressive ventricular expansion, myocardial hypertrophy, fibrosis, cardiac performance deterioration and re-expression of foetal genes. 4,5 This process involves a dynamic change of many unknown genes, proteins and signalling molecules, thereby limiting the efficacious therapy of HF.…”

Section: Introductionmentioning

confidence: 99%

Activated FMS‐like tyrosine kinase 3 ameliorates angiotensin II‐induced cardiac remodelling

Liang

Zhan

et al. 2020

Acta Physiologica

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Aim FMS‐like receptor tyrosine kinase 3 (Flt3) has been reported to be increased in cardiomyocytes responding to ischaemic stress. This study was to determine whether Flt3 activation could ameliorate pressure overload‐induced heart hypertrophy and fibrosis, and to elucidate the mechanisms of action. Methods In vivo cardiac hypertrophy and remodelling experiments were conducted by infusing angiotensin II (Ang II) chronically in male C57BL/6 mice. Flt3‐specific ligand (FL) was administered intraperitoneally every two days (5 µg/mouse). In vitro experiments on hypertrophy, apoptosis and autophagy mechanism were performed in neonatal rat cardiomyocytes (NRCMs) and H9c2 cells with adenovirus vector‐mediated overexpression of Flt3. Results Our results demonstrated that following chronic Ang II infusion for 4 weeks, the mice exhibited heart hypertrophy, fibrosis, apoptosis and contractile dysfunction. Meanwhile, Ang II induced autophagic responses in mouse hearts, as evidenced by increased LC3 II and decreased P62 expression. These pathological alterations in Ang II‐treated mice were significantly ameliorated by Flt3 activation with FL administration. In NRCMs and Flt3‐overexpressed H9c2 cells, FL attenuated Ang II‐induced pathological autophagy and inactivated AMPK/mTORC1/FoxO3a signalling, thereby efficiently mitigating cell hypertrophy and apoptosis. Conversely, the AMPK activator metformin or the mTORC1 inhibitor rapamycin reversed the effects of FL on the alterations of autophagy, hypertrophy and apoptosis in cardiomyocytes induced by Ang II. Conclusion Flt3 activation ameliorates cardiac hypertrophy, fibrosis and contractile dysfunction in the mouse model of chronic pressure overload, most likely via suppressing AMPK/mTORC1/FoxO3a‐mediated autophagy. These results provide new evidence supporting Flt3 as a novel therapeutic target in maladaptive cardiac remodelling.

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“…Therefore, pharmacological interventions targeting these signaling pathways may provide promising approaches for preventing cardiac hypertrophy. Unfortunately, despite the clinical use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and β-blockers, the death rate due to heart failure is increasing every year [2]. Thus, a better understanding of the intracellular signaling pathways that mediate cardiac hypertrophy and identification of novel drugs that disrupt the intracellular signaling pathways are greatly needed.…”

Section: Introductionmentioning

confidence: 99%

“…Generally, during hypertrophy, myocytes grow in size and contribute to protein synthesis [2]. Although this response may be initially beneficial, sustained cardiac hypertrophy ultimately leads to ventricular dilation and congestive heart failure [3].…”

Section: Introductionmentioning

confidence: 99%

Hyperoside Protects Against Pressure Overload-Induced Cardiac Remodeling via the AKT Signaling Pathway

Wang

Liu

Xiao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cardiac hypertrophy is a major predisposing factor for heart failure and sudden cardiac death. Hyperoside (Hyp), a flavonoid isolated from Rhododendron ponticum L., is a primary component of Chinese traditional patent medicines. Numerous studies have shown that Hyp exerts marked anti-viral, anti-inflammatory, anti-oxidant, anti-cancer, anti-ischemic, and particularly cardio-protective effects. However, the effects of Hyp on cardiac hypertrophy have not been explored. The aims of this study were to determine whether Hyp could protect against cardiac remodeling and to clarify the potential molecular mechanisms. Methods: Neonatal rat cardiac myocytes were isolated and treated with different concentrations of Hyp, then cultured with angiotensin II for 48 h. Mice were subjected to either aortic banding or sham surgery (control group). One week after surgery, the mice were treated with Hyp (20 mg/kg/day) or vehicle by oral gavage for 7 weeks. Hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, histology, and biomarkers. Results: Hyp pretreatment suppressed angiotensin II-induced hypertrophy in cardiomyocytes. Hyp exerted no basal effects but attenuated cardiac hypertrophy and dysfunction, fibrosis, inflammation, and oxidative stress induced by pressure overload. Both in vivo and in vitro experiments demonstrated that the effect of Hyp on cardiac hypertrophy was mediated by blocking activation of the AKT signaling pathway. Conclusion: Hyp improves cardiac function and prevents the development of cardiac hypertrophy via AKT signaling. Our results suggest a protective effect of Hyp on pressure overload-induced cardiac remodeling. Taken together, Hyp may have a role in the pharmacological therapy of cardiac hypertrophy.

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Mechanisms contributing to cardiac remodelling

Cited by 167 publications

References 258 publications

Andrographolide Protects against Aortic Banding-Induced Experimental Cardiac Hypertrophy by Inhibiting MAPKs Signaling

Andrographolide Protects against Aortic Banding-Induced Experimental Cardiac Hypertrophy by Inhibiting MAPKs Signaling

Activated FMS‐like tyrosine kinase 3 ameliorates angiotensin II‐induced cardiac remodelling

Hyperoside Protects Against Pressure Overload-Induced Cardiac Remodeling via the AKT Signaling Pathway

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