Inhibition of AP-1 signaling by JDP2 overexpression protects cardiomyocytes against hypertrophy and apoptosis induction

Hill, Christian; Würfel, Alona; Heger, Jacqueline; Meyering, Bettina; Schlüter, Klaus‐Dieter; Weber, Martin; Ferdinándy, Péter; Aronheim, Ami; Schulz, Rainer; Euler, Gerhild

doi:10.1093/cvr/cvt094

Cited by 37 publications

(36 citation statements)

References 16 publications

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“…That AP‐1 is a mediator of hypertrophy and apoptosis in β‐adrenoceptor stimulated cardiomyocytes has been shown by use of transgenic mice overexpressing the AP‐1 inhibitor jun dimerization protein 2 (JDP2). JDP2 overexpression prevented isoprenaline (ISO)‐induced hypertrophy as well as TGFβ‐induced apoptosis in cardiomyocytes (Hill et al ., ). But AP‐1 is also required to preserve the contractile function of cardiomyocytes because AP‐1 inhibition by JDP2 overexpression attenuated contractile responses induced by β‐adrenoceptor stimulation (Hill et al ., ).…”

Section: The Tak1 Pathway Is Pro‐hypertrophic and Prevents Cell Deathmentioning

confidence: 97%

Molecular switches under TGFβ signalling during progression from cardiac hypertrophy to heart failure

Heger

Schulz

Euler

2015

British J Pharmacology

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Cardiac hypertrophy is a mechanism to compensate for increased cardiac work load, that is, after myocardial infarction or upon pressure overload. However, in the long run cardiac hypertrophy is a prevailing risk factor for the development of heart failure. During pathological remodelling processes leading to heart failure, decompensated hypertrophy, death of cardiomyocytes by apoptosis or necroptosis and fibrosis as well as a progressive dysfunction of cardiomyocytes are apparent. Interestingly, the induction of hypertrophy, cell death or fibrosis is mediated by similar signalling pathways. Therefore, tiny changes in the signalling cascade are able to switch physiological cardiac remodelling to the development of heart failure. In the present review, we will describe examples of these molecular switches that change compensated hypertrophy to the development of heart failure and will focus on the importance of the signalling cascades of the TGFβ superfamily in this process. In this context, potential therapeutic targets for pharmacological interventions that could attenuate the progression of heart failure will be discussed.

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Section: The Tak1 Pathway Is Pro‐hypertrophic and Prevents Cell Deathmentioning

confidence: 97%

Molecular switches under TGFβ signalling during progression from cardiac hypertrophy to heart failure

Heger

Schulz

Euler

2015

British J Pharmacology

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“…Moreover, according to previous studies, the expression of AP‐1 is increased by the JAK2/STAT3 pathway, which is associated with inflammation and cardiac hypertrophy. However, according to Hill et al study, the expression of AP‐1 is necessary for cardiac contractile function, and nonexpression of it is associated with contractile dysfunction in cardiac cells (Hill et al, ). Furthermore, the mentioned study showed that the activation of JAK2/STAT3 resulted in the prevention of apoptosis by HSF1.…”

Section: Discussion and Future Perspectivementioning

confidence: 99%

Protective role of heat shock transcription factor 1 in heart failure: A diagnostic approach

Haybar

Shahrabi

Rezaeeyan

et al. 2018

Journal Cellular Physiology

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Objective Nonexpression or expression inhibition of protective factors has been determined in the occurrence of heart failure (HF). Heat shock transcription factor 1 (HSF1) is among such factors, which reduces the incidence of HF by controlling cardiac hypertrophy and fibrosis. In this study, molecular mechanisms for nonexpression of HSF1 in HF patients have been investigated. Materials and methods This review paper is based on the material obtained via PubMed search of 1996–2018. The key search terms were "heart failure," "heat shock transcription factor 1," "hypertrophy", "fibrosis," and "apoptosis." Results Although factors such as janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and heat shock proteins (HSPs) may respectively increase and decrease susceptibility to HF, in some circumstances, these factors may unexpectedly prevent HF progression. Conclusion Finally, identification of molecular pathways expressed by various factors could be used to design appropriate treatments or to employ strategies inducing the expression of HSF1 to prevent HF.

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“…56,63 Replicating variations of in vivo phenotypes, the size, contractility, and electrophysiology of neoCMs in culture are known to vary during the first 7 d after isolation. 53−55 When compared to rat neoCMs, the variation of in vitro physiological phenotypes of mouse neoCMs is less dependent on serum growth factors, 54 involving an increase with time in the contractility rate, 64 contraction velocities, 65 and a decrease of times of contraction. 65 Such changes are not observed with our microsposts treated with Plasma and GPTMS laminin .…”

Section: Discussionmentioning

confidence: 99%

“…53−55 When compared to rat neoCMs, the variation of in vitro physiological phenotypes of mouse neoCMs is less dependent on serum growth factors, 54 involving an increase with time in the contractility rate, 64 contraction velocities, 65 and a decrease of times of contraction. 65 Such changes are not observed with our microsposts treated with Plasma and GPTMS laminin . The higher stability of APTES glut-laminin -mediated cell anchorage increases the efficiency of force transfer to posts in the long term, which may lead to the occurrence of in vivo contractile phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Stable, Covalent Attachment of Laminin to Microposts Improves the Contractility of Mouse Neonatal Cardiomyocytes

Ribeiro¹,

Zaleta-Rivera

Ashley

et al. 2014

ACS Appl. Mater. Interfaces

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The mechanical output of contracting cardiomyocytes, the muscle cells of the heart, relates to healthy and disease states of the heart. Culturing cardiomyocytes on arrays of elastomeric microposts can enable inexpensive and high-throughput studies of heart disease at the single-cell level. However, cardiomyocytes weakly adhere to these microposts, which limits the possibility of using biomechanical assays of single cardiomyocytes to study heart disease. We hypothesized that a stable covalent attachment of laminin to the surface of microposts improves cardiomyocyte contractility. We cultured cells on polydimethylsiloxane microposts with laminin covalently bonded with the organosilanes 3-glycidoxypropyltrimethoxysilane and 3-aminopropyltriethoxysilane with glutaraldehyde. We measured displacement of microposts induced by the contractility of mouse neonatal cardiomyocytes, which attach better than mature cardiomyocytes to substrates. We observed time-dependent changes in contractile parameters such as micropost deformation, contractility rates, contraction and relaxation speeds, and the times of contractions. These parameters were affected by the density of laminin on microposts and by the stability of laminin binding to micropost surfaces. Organosilane-mediated binding resulted in higher laminin surface density and laminin binding stability. 3-glycidoxypropyltrimethoxysilane provided the highest laminin density but did not provide stable protein binding with time. Higher surface protein binding stability and strength were observed with 3-aminopropyltriethoxysilane with glutaraldehyde. In cultured cardiomyocytes, contractility rate, contraction speeds, and contraction time increased with higher laminin stability. Given these variations in contractile function, we conclude that binding of laminin to microposts via 3-aminopropyltriethoxysilane with glutaraldehyde improves contractility observed by an increase in beating rate and contraction speed as it occurs during the postnatal maturation of cardiomyocytes. This approach is promising for future studies to mimic in vivo tissue environments.

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Inhibition of AP-1 signaling by JDP2 overexpression protects cardiomyocytes against hypertrophy and apoptosis induction

Cited by 37 publications

References 16 publications

Molecular switches under TGFβ signalling during progression from cardiac hypertrophy to heart failure

Molecular switches under TGFβ signalling during progression from cardiac hypertrophy to heart failure

Protective role of heat shock transcription factor 1 in heart failure: A diagnostic approach

Stable, Covalent Attachment of Laminin to Microposts Improves the Contractility of Mouse Neonatal Cardiomyocytes

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