Good and bad sides of TGFβ-signaling in myocardial infarction

Euler, Gerhild

doi:10.3389/fphys.2015.00066

Cited by 55 publications

(50 citation statements)

References 49 publications

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“…Although several Smad pathways have been reported, the canonical Smad pathway, including Smad2 and Smad3, is regarded as the primary pathway of TGF-b signaling. 38 As mentioned above, the mRNA expression levels of the TGF-b1 gene and downstream fibrosis-related genes during the remodeling phase were significantly lower in the MI+EPA group than in the MI+PBS group ( Figure 4A through 4C). To determine whether EPA treatment had an impact on TGF-b activity in vivo during the post-MI chronic phase, levels of Smad2 and Smad3, as transcription factors of the canonical Smad pathway, were determined by Western blotting.…”

Section: Tgf-b/smad Signaling Was Attenuated In the Epa-treated Mice mentioning

confidence: 55%

“…In the heart several cell types, including cardiomyocytes, endothelial cells, fibroblasts, and macrophages, release TGF-b1. 38 In addition, EPA prevented the upregulation of the protein and mRNA expression level of TGF-b1 in cultured cardiomyocytes after treatment with endothelin-1. 52 As a result, we believe that in our study, the altered TGF-b1 expression level 28 days after MI was not due to macrophages but, rather, to cardiomyocytes.…”

Section: Discussionmentioning

confidence: 98%

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Long‐Term Administration of Eicosapentaenoic Acid Improves Post–Myocardial Infarction Cardiac Remodeling in Mice by Regulating Macrophage Polarization

Takamura

Kurokawa

Ootsuji

et al. 2017

JAHA

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BackgroundConsumption of n‐3 fatty acids reduces the incidence of cardiovascular mortality in populations that consume diets rich in fish oil. Eicosapentaenoic acid (EPA) is an n‐3 fatty acid known to reduce the frequency of nonfatal coronary events; however, the frequency of mortality after myocardial infarction (MI) is not reduced. The aims of this study were to determine whether long‐term administration of EPA regulated cardiac remodeling after MI and to elucidate the underlying therapeutic mechanisms of EPA.Methods and ResultsC57BL/6J mice were divided into control (phosphate‐buffered saline–treated) and EPA‐treated groups. After 28 days of treatment, the mice were subjected to either sham surgery or MI by left anterior descending coronary artery ligation. Mortality due to MI or heart failure was significantly lower in the EPA‐treated mice than in the phosphate‐buffered saline–treated mice. However, the incidence of cardiac rupture was comparable between the EPA‐treated mice and the phosphate‐buffered saline–treated mice after MI. Echocardiographic tests indicated that EPA treatment attenuated post‐MI cardiac remodeling by preventing issues such as left ventricular systolic dysfunction and left ventricle dilatation 28 days after MI induction. Moreover, during the chronic remodeling phase, ie, 28 days after MI, flow cytometry demonstrated that EPA treatment significantly inhibited polarization toward proinflammatory M1 macrophages, but not anti‐inflammatory M2 macrophages, in the infarcted heart. Furthermore, EPA treatment attenuated fibrosis in the noninfarcted remote areas during the chronic phase.ConclusionsLong‐term administration of EPA improved the prognosis of and attenuated chronic cardiac remodeling after MI by modulating the activation of proinflammatory M1 macrophages.

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Section: Tgf-b/smad Signaling Was Attenuated In the Epa-treated Mice mentioning

confidence: 55%

Section: Discussionmentioning

confidence: 98%

Long‐Term Administration of Eicosapentaenoic Acid Improves Post–Myocardial Infarction Cardiac Remodeling in Mice by Regulating Macrophage Polarization

Takamura

Kurokawa

Ootsuji

et al. 2017

JAHA

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“…This mechanism is well-established in congestive heart failure, and ischemic heart disease. It is recognized as a predictor of adverse prognosis [11]. …”

Section: Introductionmentioning

confidence: 99%

Early Fluid Resuscitation by Lactated Ringer’s Solution Alleviate the Cardiac Apoptosis in Rats with Trauma-Hemorrhagic Shock

et al. 2016

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Cardiac trauma has been recognized as a complication associated with blunt chest trauma involving coronary artery injury, myocardium contusion and myocardial rupture. Secondary cardiac injuries after trauma supposed to be a critical factor in trauma patients, but the mechanism is not fully explored. Overproduction of TNF-alpha had been reported in multiple trauma animals, this induces oxidative stress resulting in cardiac apoptosis. Apoptosis gradually increases after trauma and reaches to a maximum level in 12 h time. TNF-alpha increases the expression of NFkB, and induces the expression of caspase-3 and resulted in cell apoptosis. The effect can be attenuated by non-selective caspase inhibitor and IL10. Fas induced cardiac apoptosis and hypertrophy in ischemic heart disease. In this study, we demonstrated a trauma-hemorrhagic shock (THS) model in rats and resuscitated rats by lactated Ringer’s (L/R) solution after shock in different hours (0 hour, 4 hours, 8 hours). NFkB gradually increased after the first 8 hours of shock, and can be reduced by fluid resuscitation. NFkB is known as a downstream pathway of Fas related apoptosis, we found Fas ligand, caspase-8 levels elevate after shock, and can be reduced by resuscitation. In addition, resuscitation can activate insulin-like growth factor (IGF-1)/Akt pathway, at the same time. It can block mitochondrial damage by decrease the effect of tBid. In conclusion, THS can induce secondary cardiac injury. Fas showed to be an important element in caspase cascade induced myocardium apoptosis. By L/R fluid resuscitation, the suppression of caspase cascade and activation of IGF-I/Akt pathway showed antiapoptotic effects in traumatic heart of rats.

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“…TGF-␤ has been reported to play an important role in heart disease (33). TGF-␤ signaling is responsible for cardiomyocyte apoptosis and cardiac hypertrophy, and TGF-␤ also promotes myofibroblast formation and extracellular matrix (ECM) production, which leads to cardiac fibrosis (34)(35)(36). In addition, our lab has newly bought mice in which the CSIG gene has been conditionally knocked out from cardiac muscle.…”

Section: Discussionmentioning

confidence: 99%

The Cellular Senescence-Inhibited Gene Is Essential for PPM1A Myristoylation To Modulate Transforming Growth Factor β Signaling

Zhu

Xie

Jiang

et al. 2018

Molecular and Cellular Biology

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The cellular senescence-inhibited gene (CSIG) is implicated in important biological processes, including cellular senescence and apoptosis. Our work showed that CSIG is involved in the myristoylation of the serine/threonine protein phosphatase PPM1A. Previous research has shown that myristoylation is necessary for PPM1A to dephosphorylate Smad2 and Smad3. However, the control and the biological significance of the myristoylation remain poorly understood. In this study, we found that CSIG knockdown disturbs PPM1A myristoylation and reduces the dephosphorylation by PPM1A of its substrate Smad2. By regulating PPM1A myristoylation, CSIG is involved in modulating the signaling of transforming growth factor β (TGF-β). Further study of the mechanism indicated that CSIG facilitates the interaction between -myristoyltransferase 1 (NMT1) and PPM1A. Taking the data together, we found that CSIG is a regulator of PPM1A myristoylation and TGF-β signaling. By promoting the myristoylation of PPM1A, CSIG enhanced the phosphatase activity of PPM1A and further inhibited TGF-β signaling. This work not only extends the biological significance of CSIG but also provides new ideas and a reference for the study of the regulatory mechanism of myristoylation.

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Good and bad sides of TGFβ-signaling in myocardial infarction

Cited by 55 publications

References 49 publications

Long‐Term Administration of Eicosapentaenoic Acid Improves Post–Myocardial Infarction Cardiac Remodeling in Mice by Regulating Macrophage Polarization

Long‐Term Administration of Eicosapentaenoic Acid Improves Post–Myocardial Infarction Cardiac Remodeling in Mice by Regulating Macrophage Polarization

Early Fluid Resuscitation by Lactated Ringer’s Solution Alleviate the Cardiac Apoptosis in Rats with Trauma-Hemorrhagic Shock

The Cellular Senescence-Inhibited Gene Is Essential for PPM1A Myristoylation To Modulate Transforming Growth Factor β Signaling

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