scholarly journals PL - 027 Up-regulation of NRG1 improves cardiac repair in zebra fish and involved in the cardioprotective effects of exercise training in rats of myocardial infarction

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Mengxin Cai ◽  
Shaojun Du ◽  
Zhenjun Tian
Keyword(s):  
Myocardial Infarction ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Cardiac Function ◽  
Signaling Pathway ◽  
Heart Development ◽  
Cardiac Repair ◽  
Cardiomyocyte Proliferation ◽  
Infarcted Heart ◽  
Cardioprotective Effects

Objective Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. Exercise training could improve cardiac function following MI. However, the mechanisms are still not well-known. Neuregulin 1 (NRG1)plays an important role in heart development and regeneration.In this study, we investigated the effect of NRG1 on cardiac regeneration in a zebrafish model, detected whether exercise could improve cardiac function through regulating NRG1 expression in infarcted heart and explore the possible role of up-regulation of NRG1 in skeletal muscle play in the cardioprotective effects in rats with MI. Methods Transgenic zebrafish line, cmlc2:CreERandβ-act2:BSNrg1,wereusedto study the effect of NRG1 on heart growth and regeneration after injury. PCNA was detected by immunofluorescence staining andmRNAexpression of gata4, nkx2.5, tbx5, smyd1b, hsp90α and murf were tested by RT-PCR.Sprague-Dawley rats were used to establish MI model and underwent fourweeks of exercise training (ET) or pAAV-{dMCK promoter}rNRG1-eGFP intervention.AG1478 was used asan inhibitor of NRG1/ErbBs signaling pathway. Cardiac function and structure,cardiomyocyte proliferation and NRG1 expression were detected in the heart or skeletal. Results Cardiac-specific overexpression of NRG1 induced cardiac hypertrophy and cardiomyocyte proliferation, regulated the mRNA expression of gata4, nkx2.5, tbx5, smyd1b, hsp90α andmurf in uninjuriedzebrafish, and promote cardiac repair and regeneration after injury in the zebrafish.Exercise activated NRG1/ErbBs signaling pathway, improved cardiac remodeling and heart function, enhanced cardiomyocyte proliferation, reduced cardiomyocyte apoptosis, ROS level and MuRF1 protein expression in rats with MI. BlockingErbB signaling attenuated the ET-induced cardioprotection effects in rat with MI.up-regulation of NRG1 expression in skeletal muscle could increase the protein level of NRG1 in serum and infarcted heart, improve cardiomyocyte proliferation and reduce the level of cardiac fibrosis, finally promote cardiac function. Conclusions Up-regulation of NRG1 expression in the heart or skeletal musclemay be one of the underlying mechanisms of thebeneficial effects of exercise training following MI.

scholarly journals Exercise Training Alleviates Cardiac Fibrosis through Increasing Fibroblast Growth Factor 21 and Regulating TGF-β1-Smad2/3-MMP2/9 Signaling in Mice with Myocardial Infarction

2021 ◽  
Vol 22 (22) ◽  
pp. 12341
Author(s):  
Yixuan Ma ◽  
Yixin Kuang ◽  
Wenyan Bo ◽  
Qiaoqin Liang ◽  
Wenfei Zhu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Growth Factor ◽  
Exercise Training ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Cardiac Fibrosis ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Infarcted Heart ◽  
Tgf Β1

Exercise training has been reported to alleviate cardiac fibrosis and ameliorate heart dysfunction after myocardial infarction (MI), but the molecular mechanism is still not fully clarified. Fibroblast growth factor 21 (FGF21) exerts a protective effect on the infarcted heart. This study investigates whether exercise training could increase FGF21 protein expression and regulate the transforming growth factor-β1 (TGF-β1)-Smad2/3-MMP2/9 signaling pathway to alleviate cardiac fibrosis following MI. Male wild type (WT) C57BL/6J mice and Fgf21 knockout (Fgf21 KO) mice were used to establish the MI model and subjected to five weeks of different types of exercise training. Both aerobic exercise training (AET) and resistance exercise training (RET) significantly alleviated cardiac dysfunction and fibrosis, up-regulated FGF21 protein expression, inhibited the activation of TGF-β1-Smad2/3-MMP2/9 signaling pathway and collagen production, and meanwhile, enhanced antioxidant capacity and reduced cell apoptosis in the infarcted heart. In contrast, knockout of Fgf21 weakened the cardioprotective effects of AET after MI. In vitro, cardiac fibroblasts (CFs) were isolated from neonatal mice hearts and treated with H2O2 (100 μM, 6 h). Recombinant human FGF21 (rhFGF21, 100 ng/mL, 15 h) and/or 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR, 1 mM, 15 h) inhibited H2O2-induced activation of the TGF-β1-Smad2/3-MMP2/9 signaling pathway, promoted CFs apoptosis and reduced collagen production. In conclusion, exercise training increases FGF21 protein expression, inactivates the TGF-β1-Smad2/3-MMP2/9 signaling pathway, alleviates cardiac fibrosis, oxidative stress, and cell apoptosis, and finally improves cardiac function in mice with MI. FGF21 plays an important role in the anti-fibrosis effect of exercise training.

Abstract 371: The Role of Survivin in Cardiac Regeneration

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Tien-Jui Tsang
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cell Apoptosis ◽  
Heart Development ◽  
Cardiac Regeneration ◽  
Border Zone ◽  
Cardiomyocyte Proliferation ◽  
Intramyocardial Injection ◽  
Infarct Region

Heart failure continues to be the major cause of mortality in many countries. How to reduce the loss of cardiac function after injury continues to be a major challenge in cardioprotective treatment. Survivin (SVV) is the smallest member in IAP (Inhibitor of apoptosis) family and has multiple functions such as inhibiting cell apoptosis and enhancing cell proliferation. SVV expresses in nucleus of proliferating cardiomyocyte during heart development but disappear in adult stage. However after injury, SVV is induced in the cytoplasm of cardiomyocyte in peri-infarct region. We established inducible conditional SVV knockout transgenic mouse to investigate the importance of SVV after myocardial infarction. Cardiac-specific SVV knockout mice exhibit poor cardiac function and more apoptotic cardiomyocytes compared to wild-type mice after injury. In order to confirm localization is related to the function of SVV, we have established adenovirus carrying SVV or SVV fused with NLS (nuclear-localization signal). SVV locates in cytoplasm after virus infection but NLS-SVV could be detected in both cytoplasm and nucleus. Both SVV and NLS-SVV inhibited cell apoptosis in vitro but only NLS-SVV enhanced neonatal mouse cardiomyocyte proliferation. Mice received intramyocardial injection of virus shows better ejection fraction after myocardial infarction and less apoptotic cardiomyocytes in peri-infarct region, and more H3P-positive cardiomyocytes are observed in border zone overexpressing NLS-SVV group. We believe this dual functional SVV can be applied in future cardioprotective therapy.

scholarly journals Cardioprotective effects of Ginsenoside compound-Mc1 and Dendrobium Nobile Lindl against myocardial infarction in an aged rat model: Involvement of TLR4/NF-κB signaling pathway

2021 ◽  
Vol 19 ◽  
pp. 205873922110005
Author(s):  
Yongle Sun ◽  
Jing Geng ◽  
Deyu Wang
Keyword(s):  
Myocardial Infarction ◽  
Combination Therapy ◽  
Infarct Size ◽  
Signaling Pathway ◽  
Left Ventricular ◽  
Male Rats ◽  
Dendrobium Nobile ◽  
Tnf Α ◽  
Cardioprotective Effects ◽  
Dendrobium Nobile Lindl

Aging is the crucial co-morbidity that prevents the full cardioprotection against myocardial ischemia/reperfusion (I/R) injury. Combination therapy as a promising strategy may overcome this clinical problem. This study aimed to investigate the cardioprotective effects of Ginsenoside compound-Mc1 (GMc1) and Dendrobium Nobile Lindl (DNL) in myocardial I/R injury and explore the involvement of the TLR4/NF-κB signaling pathway in aged rats. In vivo I/R injury and myocardial infarction was established by temporary coronary ligation in 22–24 months’ old Sprague Dawley male rats. GMc1 (10 mg/kg) and DNL (80 mg/kg) were administered intraperitoneally for 4 weeks and orally for 14 days, respectively, before I/R injury. Infarct size was measured through triphenyl-tetrazolium-chloride staining. ELISA assay was conducted to quantify the levels of cardiotroponin, and myocardial content of TNF-α and glutathione. Western blotting was employed to detect the expression of TLR4/MyD88/NF-κB proteins. GMc1 and DNL significantly reduced the infarct size to a similar extent ( p < 0.05) but their combined effect was greater than individual ones ( p < 0.01). Combination therapy significantly restored the left ventricular end-diastolic and developed pressures at the end of reperfusion as compared with the untreated group ( p < 0.01). Although the GMc1 and DNL reduced the levels of inflammatory cytokine TNF-α and increased the contents of antioxidant glutathione significantly, their individual effects on the reduction of protein expression of TLR4/MyD88/NF-κB pathway were not consistent. However, their combination could significantly reduce all parameters of this inflammatory pathway as compared to untreated I/R rats ( p < 0.001). Therefore, the combined treatment with GMc1 and DNL increased the potency of each intervention in protecting the aged hearts against I/R injury. Reduction in the activity of the TLR4/MyD88/NF-κB signaling pathway and subsequent modulation of the activity of inflammatory cytokines and endogenous antioxidants play an important role in this cardioprotection.

scholarly journals Blockade of the Notch Signaling Pathway Promotes M2 Macrophage Polarization to Suppress Cardiac Fibrosis Remodeling in Mice With Myocardial Infarction

2022 ◽  
Vol 8 ◽  
Author(s):  
Zhi Li ◽  
Miao Nie ◽  
Liming Yu ◽  
Dengshun Tao ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cardiac Fibrosis ◽  
Macrophage Polarization ◽  
Notch Signaling Pathway ◽  
Inflammatory Factors ◽  
M2 Macrophage ◽  
M2 Polarization

Myocardial infarction (MI) is regarded as a serious ischemic heart disease on a global level. The current study set out to explore the mechanism of the Notch signaling pathway in the regulation of fibrosis remodeling after the occurrence of MI. First, experimental mice were infected with recombination signal binding protein J (RBP-J) shRNA and empty adenovirus vector, followed by the establishment of MI mouse models and detection of cardiac function. After 4 weeks of MI, mice in the sh-RBP-J group were found to exhibit significantly improved cardiac function relative to the sh-NC group. Moreover, knockdown of RBP-J brought about decreased infarct area, promoted cardiac macrophages M2 polarization, reduced cardiac fibrosis, and further decreased transcription and protein expressions of inflammatory factors and fibrosis-related factors. Furthermore, downregulation of cylindromatosis (CYLD) using si-CYLD reversed the results that knockdown of RBP-J inhibited fibrogenesis and the release of inflammatory factors. Altogether, our findings indicated that the blockade of Notch signaling promotes M2 polarization of cardiac macrophages and improves cardiac function by inhibiting the imbalance of fibrotic remodeling after MI.

scholarly journals Short-term exercise training improves cardiac function associated to a better antioxidant response and lower type 3 iodothyronine deiodinase activity after myocardial infarction

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0222334
Author(s):  
Rafael Aguiar Marschner ◽  
Patrícia Banda ◽  
Simone Magagnin Wajner ◽  
Melissa Medeiros Markoski ◽  
Maximiliano Schaun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Exercise Training ◽  
Cardiac Function ◽  
Antioxidant Response ◽  
Short Term ◽  
Iodothyronine Deiodinase ◽  
Lower Type ◽  
Deiodinase Activity ◽  
Type 3

scholarly journals Intercalated disc protein Xinβ is required for Hippo-YAP signaling in the heart

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Haipeng Guo ◽  
Yao Wei Lu ◽  
Zhiqiang Lin ◽  
Zhan-Peng Huang ◽  
Jianming Liu ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiac Function ◽  
Heart Development ◽  
Genetic Interaction ◽  
Specific Cell ◽  
Cardiomyocyte Proliferation ◽  
Intercalated Disc ◽  
Knock Out ◽  
Genes Encoding ◽  
Knock Out Mice

Abstract Intercalated discs (ICD), specific cell-to-cell contacts that connect adjacent cardiomyocytes, ensure mechanical and electrochemical coupling during contraction of the heart. Mutations in genes encoding ICD components are linked to cardiovascular diseases. Here, we show that loss of Xinβ, a newly-identified component of ICDs, results in cardiomyocyte proliferation defects and cardiomyopathy. We uncovered a role for Xinβ in signaling via the Hippo-YAP pathway by recruiting NF2 to the ICD to modulate cardiac function. In Xinβ mutant hearts levels of phosphorylated NF2 are substantially reduced, suggesting an impairment of Hippo-YAP signaling. Cardiac-specific overexpression of YAP rescues cardiac defects in Xinβ knock-out mice—indicating a functional and genetic interaction between Xinβ and YAP. Our study reveals a molecular mechanism by which cardiac-expressed intercalated disc protein Xinβ modulates Hippo-YAP signaling to control heart development and cardiac function in a tissue specific manner. Consequently, this pathway may represent a therapeutic target for the treatment of cardiovascular diseases.

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