Pressure Overload-Induced Cardiac Hypertrophy Response Requires Janus Kinase 2-Histone Deacetylase 2 Signaling

Huang, Ying; Tan, Jing‐Hua; Jing-hua, Shen; Wang, Hao; Dai-fu, Zhang

doi:10.3390/ijms151120240

Cited by 6 publications

(4 citation statements)

References 31 publications

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“…Angiotensin II (Ang II), a potent stimulus of cardiac myocyte growth factors, has been found to be elevated in cardiac failure ( Zucker et al, 2015 ). Ang II can be used to mimic pressure-overload-induced cardiac hypertrophy ( Ying et al, 2014 ) and has been widely employed as a hypertrophic stimulus in various in vitro cardiac disease models ( Ding et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Parkia speciosa Hassk. Empty Pod Extract Alleviates Angiotensin II-Induced Cardiomyocyte Hypertrophy in H9c2 Cells by Modulating the Ang II/ROS/NO Axis and MAPK Pathway

et al. 2021

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Cardiac hypertrophy is characteristic of heart failure in patients who have experienced cardiac remodeling. Many medicinal plants, including Parkia speciosa Hassk., have documented cardioprotective effects against such pathologies. This study investigated the activity of P. speciosa empty pod extract against cardiomyocyte hypertrophy in H9c2 cardiomyocytes exposed to angiotensin II (Ang II). In particular, its role in modulating the Ang II/reactive oxygen species/nitric oxide (Ang II/ROS/NO) axis and mitogen-activated protein kinase (MAPK) pathway was examined. Treatment with the extract (12.5, 25, and 50 μg/ml) prevented Ang II-induced increases in cell size, NADPH oxidase activity, B-type natriuretic peptide levels, and reactive oxygen species and reductions in superoxide dismutase activity. These were comparable to the effects of the valsartan positive control. However, the extract did not significantly ameliorate the effects of Ang II on inducible nitric oxide synthase activity and nitric oxide levels, while valsartan did confer such protection. Although the extract decreased the levels of phosphorylated extracellular signal-related kinase, p38, and c-Jun N-terminal kinase, valsartan only decreased phosphorylated c-Jun N-terminal kinase expression. Phytochemical screening identified the flavonoids rutin (1) and quercetin (2) in the extract. These findings suggest that P. speciosa empty pod extract protects against Ang II-induced cardiomyocyte hypertrophy, possibly by modulating the Ang II/ROS/NO axis and MAPK signaling pathway via a mechanism distinct from valsartan.

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Section: Introductionmentioning

confidence: 99%

Parkia speciosa Hassk. Empty Pod Extract Alleviates Angiotensin II-Induced Cardiomyocyte Hypertrophy in H9c2 Cells by Modulating the Ang II/ROS/NO Axis and MAPK Pathway

et al. 2021

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“…The beneficial effects of metformin on cardiac function have been attributed to direct actions on cell metabolism, endothelial function, platelet reactivity and calcium homeostasis (25). Since hypertrophic stimuli, including angiotensin II and pressure overload, may increase the expression of ANP and BNP (26), the mRNA levels of ANP and BNP following metformin and/or Ang II treatment were investigated as hypertrophic markers in the present study. The results revealed that metformin significantly suppressed the development of Ang II-induced cardiomyocyte hypertrophy as evidenced by reductions in cardiomyocyte surface area, reduced expression of hypertrophy-associated genes ANP and BNP in Ang II-stimulated cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

Metformin attenuates angiotensin II‑induced cardiomyocyte hypertrophy by upregulating the MuRF1 and MAFbx pathway

Cao

Yan

et al. 2021

Exp Ther Med

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Pathological cardiac hypertrophy induced by aging and neurohumoral activation, such as angiotensin II (Ang II) activation, is an independent risk factor for heart failure. The muscle really interesting new gene-finger protein-1 (MuRF1) and muscle atrophy F-box (MAFbx) pathway has been previously reported to be an important mechanism underlying the pathogenesis of cardiac hypertrophy. Metformin is currently the first-line blood glucose-lowering agent that can be useful for the treatment of cardiovascular diseases. However, the potential role of metformin in the modulation of MuRF1 and MAFbx in cardiomyocyte hypertrophy remains poorly understood. The present study used H9c2 cells, a cardiomyocyte cell model. The surface area of cultured rat H9c2 myoblasts was measured and the expression levels of MuRF1 and MAFbx were quantified using western blot or reverse transcription-quantitative PCR. H9c2 cells were transfected with MuRF1 and MAFbx small interfering (si) RNA. The present study revealed that Ang II treatment significantly increased the cell surface area of model cardiomyocytes. Additionally, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNA and protein expression was increased following this treatment. Ang II also downregulated MuRF1 and MAFbx protein and mRNA expression. In the H9C2, treatment with metformin attenuated hypertrophic remodeling. In addition, expression of ANP and BNP was significantly reduced in metformin-treated H9C2 cells. The results indicated that metformin increased the activity of MuRF1 and MAFbx and upregulated their expression, the knockdown of which resulted in deteriorative Ang II-induced cell hypertrophy, even following treatment with metformin. Taken together, data from the present study suggest that metformin can prevent cardiac hypertrophy through the MuRF1 and MAFbx pathways.

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“…In parallel with highlighting the anti-apoptotic/anabolic pro le of the cardiac myotubes in response to different loading conditions, this study also examined the expression responses of pro-apoptotic and muscle atrophy genes to the various mechanical stimuli. While many studies have suggested potentially bene cial effects of mechanical stretching on cardiomyocytes structure and function [1,[44][45][46], nevertheless, excessive mechanical stimuli have been reported to induce cardiac cell apoptosis and maladaptive hypertrophy, which promote upregulation of atrophy and in ammation factors [7,36,47].…”

Section: Discussionmentioning

confidence: 99%

Optimizing Mechanical Stretching Protocols for Hypertrophic and Anti-apoptotic Responses in H9c2 Cardiomyocytes

Zevolis

Philippou

Moustogiannis

et al. 2020

Preprint

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Background: Cardiomyocytes are sensitive to mechanical loading, possessing the ability to respond to mechanical stimuli by reprogramming their gene expression. In this study, signaling as well as expression responses of myogenic, anabolic, inflammatory, atrophy and pro-apoptotic genes to different mechanical stretching protocols were examined in differentiated cardiomyocytes.Methods: H9C2 cardiomyoblasts were cultured on elastic membranes up to their 5th day of differentiation (myotubes) and then subjected to three different stretching protocols by altering their strain, frequency and duration characteristics, using an in vitro cell tension system. cells were harvested and lysed 24 hours after the completion of each stretching protocol and Real Time-PCR was used to monitor changes in mRNA expression of myogenic regulatory factors (MyoD, Myogenin, MRF4), the IGF-1 isoforms (IGF-1Ea, IGF-1Eb), as well as atrophy (Atrogin-1), pro-apoptotic (FoxO, Fuca), and inflammatory (IL-6) factors in response to the different mechanical loading conditions. The activation of Akt and Erk 1/2 signaling proteins following the various stretching protocols was also evaluated by Western blot analysis.Results: We documented that the low strain (2.7% elongation), low frequency (0.25 Hz) and intermediate duration (12 hrs) stretching protocol was overall the most effective in inducing beneficial responses in differentiated cardiomyoblasts as it increased the expression of IGF-1 isoforms and phosphorylation of Akt and Erk1/2 (p<0.05), while it provoked the downregulation of all the other factors examined (p<0.05-0.001). Conclusion: These findings demonstrated that a low strain, low frequency of intermediate duration stretching protocol is the most effective in inducing a hypertrophic and anti-apoptotic response in H9C2 cardiomyotubes, in vitro.

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Pressure Overload-Induced Cardiac Hypertrophy Response Requires Janus Kinase 2-Histone Deacetylase 2 Signaling

Cited by 6 publications

References 31 publications

Parkia speciosa Hassk. Empty Pod Extract Alleviates Angiotensin II-Induced Cardiomyocyte Hypertrophy in H9c2 Cells by Modulating the Ang II/ROS/NO Axis and MAPK Pathway

Parkia speciosa Hassk. Empty Pod Extract Alleviates Angiotensin II-Induced Cardiomyocyte Hypertrophy in H9c2 Cells by Modulating the Ang II/ROS/NO Axis and MAPK Pathway

Metformin attenuates angiotensin II‑induced cardiomyocyte hypertrophy by upregulating the MuRF1 and MAFbx pathway

Optimizing Mechanical Stretching Protocols for Hypertrophic and Anti-apoptotic Responses in H9c2 Cardiomyocytes

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