EZH2 controls epicardial cell migration during heart development

Jiang, Haobin; Bai, Lina; Song, Shen; Yin, Qianqian; Shi, Anteng; Zhou, Bin; Hong, Lan; Chen, Hou-Zao; Xu, Cheng‐Ran; Wang, Yanchun; Nie, Yu; Hu, Shengshou

doi:10.26508/lsa.202201765

Cited by 4 publications

(4 citation statements)

References 30 publications

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“…However, this inhibition also reduces human iCMs incidence, conflicting with heart reprogramming goals ( Tang et al, 2021 ). EZH2 is essential for epicardial cell migration by suppressing tissue inhibitor of metalloproteinase 3 (TIMP3), playing a critical role in cardiac development ( Jiang et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Role of EZH2-mediated epigenetic modification on vascular smooth muscle in cardiovascular diseases: A mini-review

Luo,

Li,

Song

et al. 2024

Front. Pharmacol.

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Vascular smooth muscle cells (VSMCs) are integral to the pathophysiology of cardiovascular diseases (CVDs). Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, plays a crucial role in epigenetic regulation of VSMCs gene expression. Emerging researches suggest that EZH2 has a dual role in VSMCs, contingent on the pathological context of specific CVDs. This mini-review synthesizes the current knowledge on the mechanisms by which EZH2 regulates VSMC proliferation, migration and survival in the context of CVDs. The goal is to underscore the potential of EZH2 as a therapeutic target for CVDs treatment. Modulating EZH2 and its associated epigenetic pathways in VSMCs could potentially ameliorate vascular remodeling, a key factor in the progression of many CVDs. Despite the promising outlook, further investigation is warranted to elucidate the epigenetic mechanisms mediated by EZH2 in VSMCs, which may pave the way for novel epigenetic therapies for conditions such as atherosclerosis and hypertension.

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Section: Discussionmentioning

confidence: 99%

Role of EZH2-mediated epigenetic modification on vascular smooth muscle in cardiovascular diseases: A mini-review

Luo,

Li,

Song

et al. 2024

Front. Pharmacol.

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“…EZH2 has also been noted to be increased in hypertrophic cardiomyocytes (Li et al, 2022), contradicting IPA's predicted expression state. However, inactivation of EZH2 resulted in congenital heart malformations due to inhibition of cardiomyocyte differentiation, proliferation, and regenerative capacity (He et al, 2012; Jiang et al, 2023). EZH2 contributes to epicardial cell migration into the myocardium, which is vital for proper heart development and generation of various cell lines (He et al, 2012; Jiang et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

“…However, inactivation of EZH2 resulted in congenital heart malformations due to inhibition of cardiomyocyte differentiation, proliferation, and regenerative capacity (He et al, 2012; Jiang et al, 2023). EZH2 contributes to epicardial cell migration into the myocardium, which is vital for proper heart development and generation of various cell lines (He et al, 2012; Jiang et al, 2023). Despite contradictory evidence for the role of EZH2 in the cardiac hypertrophy pathway, compelling evidence suggests that EZH2 is required for development of the neonatal heart.…”

Section: Discussionmentioning

confidence: 99%

Meta‐analysis reveals differential gene expression in tetralogy of Fallot versus controls

Voskamp,

Hammonds,

Knapp

et al. 2023

Birth Defects Research

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ObjectivesTetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect in the United States. We aimed to identify genetic variations associated with TOF using meta‐analysis of publicly available digital samples to spotlight targets for prevention, screening, and treatment strategies.MethodsWe used the Search Tag Analyze Resource for Gene Expression Omnibus (STARGEO) platform to identify 39 TOF and 19 non‐TOF right ventricle tissue samples from microarray data and identified upregulated and downregulated genes. Associated gene expression data were analyzed using ingenuity pathway analysis and restricted to genes with a statistically significant (p < .05) difference and an absolute experimental log ratio >0.1 between disease and control samples.ResultsOur analysis identified 220 genes whose expression profiles were significantly altered in TOF vs. non‐TOF samples. The most striking differences identified in gene expression included genes FBXO32, PTGES, MYL12a, and NR2F2. Some top associated canonical pathways included adrenergic signaling, estrogen receptor signaling, and the role of NFAT in cardiac hypertrophy. In general, genes involved in adaptive, defensive, and reparative cardiovascular responses showed altered expression in TOF vs. non‐TOF samples.ConclusionsWe introduced the interpretation of open “big data” using the STARGEO platform to define robust genomic signatures of congenital heart disease pathology of TOF. Overall, our meta‐analysis results indicated increased metabolism, inflammation, and altered gene expression in TOF patients. Estrogen receptor signaling and the role of NFAT in cardiac hypertrophy represent unique pathways upregulated in TOF patients and are potential targets for future pharmacologic treatments.

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“…[21][22][23][24][25] Studies have highlighted the importance of the ECM in modulating proliferation, migration, and differentiation during heart development and repair processes. [12][13][14][15][26][27][28] However, the specific ECM components that regulate cardiomyocyte proliferation and cardiac repair in the context of heart regeneration remain largely unidentified.…”

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confidence: 99%

Versican Promotes Cardiomyocyte Proliferation and Cardiac Repair

Feng,

Li,

et al. 2024

Circulation

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BACKGROUND: The adult mammalian heart is incapable of regeneration, whereas a transient regenerative capacity is maintained in the neonatal heart, primarily through the proliferation of preexisting cardiomyocytes. Neonatal heart regeneration after myocardial injury is accompanied by an expansion of cardiac fibroblasts and compositional changes in the extracellular matrix. Whether and how these changes influence cardiomyocyte proliferation and heart regeneration remains to be investigated. METHODS: We used apical resection and myocardial infarction surgical models in neonatal and adult mice to investigate extracellular matrix components involved in heart regeneration after injury. Single-cell RNA sequencing and liquid chromatography–mass spectrometry analyses were used for versican identification. Cardiac fibroblast–specific Vcan deletion was achieved using the mouse strains Col1a2-2A-CreER and Vcan fl/fl . Molecular signaling pathways related to the effects of versican were assessed through Western blot, immunostaining, and quantitative reverse transcription polymerase chain reaction. Cardiac fibrosis and heart function were evaluated by Masson trichrome staining and echocardiography, respectively. RESULTS: Versican, a cardiac fibroblast–derived extracellular matrix component, was upregulated after neonatal myocardial injury and promoted cardiomyocyte proliferation. Conditional knockout of Vcan in cardiac fibroblasts decreased cardiomyocyte proliferation and impaired neonatal heart regeneration. In adult mice, intramyocardial injection of versican after myocardial infarction enhanced cardiomyocyte proliferation, reduced fibrosis, and improved cardiac function. Furthermore, versican augmented the proliferation of human induced pluripotent stem cell–derived cardiomyocytes. Mechanistically, versican activated integrin β1 and downstream signaling molecules, including ERK1/2 and Akt, thereby promoting cardiomyocyte proliferation and cardiac repair. CONCLUSIONS: Our study identifies versican as a cardiac fibroblast–derived pro-proliferative proteoglycan and clarifies the role of versican in promoting adult cardiac repair. These findings highlight its potential as a therapeutic factor for ischemic heart diseases.

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EZH2 controls epicardial cell migration during heart development

Cited by 4 publications

References 30 publications

Role of EZH2-mediated epigenetic modification on vascular smooth muscle in cardiovascular diseases: A mini-review

Role of EZH2-mediated epigenetic modification on vascular smooth muscle in cardiovascular diseases: A mini-review

Meta‐analysis reveals differential gene expression in tetralogy of Fallot versus controls

Versican Promotes Cardiomyocyte Proliferation and Cardiac Repair

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