Wnt/β-catenin in ischemic myocardium: interactions and signaling pathways as a therapeutic target

Haybar, Habib; Khodadi, Elahe; Shahrabi, Saeid

doi:10.1007/s10741-018-9759-z

Cited by 36 publications

(23 citation statements)

References 70 publications

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“…Research works aimed at discovering the relationship between gene CTNNB1 expression level and various diseases had been conducted. It is reported that the gene mutations of β-catenin is capable of controlling the activation and inactivation of the pathway for the myocardium [27]. Meanwhile, a bioinformatic gene analysis has reported that the CTNNB1 was implicated in atrial fibrillation, which is considered to be one of the major causes of IS [28].…”

Section: Introductionmentioning

confidence: 99%

A 3′ Untranslated Region Polymorphism of CTNNB1 (Rs2953) Alters MiR-3161 Binding and Affects the Risk of Ischemic Stroke and Coronary Artery Disease in Chinese Han Population

Zhao

Yang

et al. 2021

Eur Neurol

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Background: CTNNB1 is reported to be related to the pathological process of ischemic stroke (IS) and coronary artery disease (CAD). Polymorphism located in the 3′ untranslated region (3′UTR) of a gene might affect gene expression by modifying binding sites for microRNAs (miRNAs). This study aimed to analyze the association between polymorphism rs2953, which locates in the 3′UTR of CTNNB1, and the risk of IS and CAD. Methods: The CTNNB1 messenger RNA (mRNA) expression level in peripheral venous blood was measured. In total, 533 patients with IS, 500 patients with CAD, and 531 healthy individuals were genotyped by Sequenom MassArray technology. The binding of miR-3161 to CTNNB1 was determined by dual-luciferase reporter assay. Results: The CTNNB1 mRNA expression level for the IS group was significantly lower than that for the control group. Rs2953 was significantly associated with both IS risk and CAD risk. Significant association was also found between polymorphism rs2953 and many conventional factors, such as serum lipid level, blood coagulation markers, blood glucose level, and homocysteine level in patients. Rs2953 T allele introduced a binding site to miRNA-3161 and thus decreased luciferase activity. Conclusion: Polymorphism rs2953 is associated with the risk of both IS and CAD. Moreover, polymorphism rs2953 (T) introduces a binding site to miRNA-3161 and thus decreases luciferase activity in cell lines.

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Section: Introductionmentioning

confidence: 99%

A 3′ Untranslated Region Polymorphism of CTNNB1 (Rs2953) Alters MiR-3161 Binding and Affects the Risk of Ischemic Stroke and Coronary Artery Disease in Chinese Han Population

Zhao

Yang

et al. 2021

Eur Neurol

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“…Wnt dysregulation has an important role in cardiac diseases such as hypertrophy and fibrosis [78]. The Wnt pathway is important in the response to heart injuries leading to adverse effects on the heart [79] and is integrated with bioenergetic status to control mTOR activity [80]. Wnt is activated in late-stage inflammation of heart tissue [81].…”

mentioning

confidence: 99%

Associated Targets of the Antioxidant Cardioprotection of Ganoderma lucidum in Diabetic Cardiomyopathy by Using Open Targets Platform: A Systematic Review

Shaher

Qiu

Wang

et al. 2020

BioMed Research International

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Even with substantial advances in cardiovascular therapy, the morbidity and mortality rates of diabetic cardiomyopathy (DCM) continually increase. Hence, a feasible therapeutic approach is urgently needed. Objectives. This work is aimed at systemically reviewing literature and addressing cell targets in DCM through the possible cardioprotection of G. lucidum through its antioxidant effects by using the Open Targets Platform (OTP) website. Methods. The OTP website version of 19.11 was accessed in December 2019 to identify the studies in DCM involving G. lucidum. Results. Among the 157 cell targets associated with DCM, the mammalian target of rapamycin (mTOR) was shared by all evidence, drug, and text mining data with 0.08 score association. mTOR also had the highest score association 0.1 with autophagy in DCM. Among the 1731 studies of indexed PubMed articles on G. lucidum published between 1985 and 2019, 33 addressed the antioxidant effects of G. lucidum and its molecular signal pathways involving oxidative stress and therefore were included in the current work. Conclusion. mTOR is one of the targets by DCM and can be inhibited by the antioxidative properties of G. lucidum directly via scavenging radicals and indirectly via modulating mTOR signal pathways such as Wnt signaling pathway, Erk1/2 signaling, and NF-κB pathways.

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“…It is quite conceivable that in the plethora of signaling taking place in the healing infarct, inhibition of WNT signaling may tip the balance toward conditions in which other pathways become active to stimulate CM proliferation. Moreover, activated WNT/b-catenin signaling in CMs is associated with a hypertrophic phenotype in vivo characterized by polyploidy/multinucleation and extensively developed contractile apparatus (Haybar et al, 2019). This phenotype could in fact hamper the completion of the cell cycle with cytokinesis, as discussed before.…”

Section: Wnt Signalingmentioning

confidence: 81%

Interventions in WNT Signaling to Induce Cardiomyocyte Proliferation: Crosstalk with Other Pathways

Blankesteijn

2019

Mol Pharmacol

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Myocardial infarction is a frequent cardiovascular event and a major cause for cardiomyocyte loss. In adult mammals, cardiomyocytes are traditionally considered to be terminally differentiated cells, unable to proliferate. Therefore, the woundhealing response in the infarct area typically yields scar tissue rather than newly formed cardiomyocytes. In the last decade, several lines of evidence have challenged the lack of proliferative capacity of the differentiated cardiomyocyte: studies in zebrafish and neonatal mammals have convincingly demonstrated the regenerative capacity of cardiomyocytes. Moreover, multiple signaling pathways have been identified in these models that-when activated in adult mammalian cardiomyocytes-can reactivate the cell cycle in these cells. However, cardiomyocytes frequently exit the cell cycle before symmetric division into daughter cells, leading to polyploidy and multinucleation. Now that there is more insight into the reactivation of the cell cycle machinery, other prerequisites for successful symmetric division of cardiomyocytes, such as the control of sarcomere disassembly to allow cytokinesis, require more investigation. This review aims to discuss the signaling pathways involved in cardiomyocyte proliferation, with a specific focus on wingless/int-1 protein signaling. Comparing the conflicting results from in vitro and in vivo studies on this pathway illustrates that the interaction with other cells and structures around the infarct is likely to be essential to determine the outcome of these interventions. The extensive crosstalk with other pathways implicated in cardiomyocyte proliferation calls for the identification of nodal points in the cell signaling before cardiomyocyte proliferation can be moved forward toward clinical application as a cure of cardiac disease. SIGNIFICANCE STATEMENT Evidence is mounting that proliferation of pre-existing cardiomyocytes can be stimulated to repair injury of the heart. In this review article, an overview is provided of the different signaling pathways implicated in cardiomyocyte proliferation with emphasis on wingless/int-1 protein signaling, crosstalk between the pathways, and controversial results obtained in vitro and in vivo.

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Wnt/β-catenin in ischemic myocardium: interactions and signaling pathways as a therapeutic target

Cited by 36 publications

References 70 publications

A 3′ Untranslated Region Polymorphism of <b><i>CTNNB1</i></b> (Rs2953) Alters MiR-3161 Binding and Affects the Risk of Ischemic Stroke and Coronary Artery Disease in Chinese Han Population

A 3′ Untranslated Region Polymorphism of <b><i>CTNNB1</i></b> (Rs2953) Alters MiR-3161 Binding and Affects the Risk of Ischemic Stroke and Coronary Artery Disease in Chinese Han Population

Associated Targets of the Antioxidant Cardioprotection of Ganoderma lucidum in Diabetic Cardiomyopathy by Using Open Targets Platform: A Systematic Review

Interventions in WNT Signaling to Induce Cardiomyocyte Proliferation: Crosstalk with Other Pathways

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