Pleiotropic cardiac functions controlled by ischemia-induced lncRNA H19

Hobuß, Lisa; Foinquinos, Ariana; Jung, Mira; Kenneweg, Franziska; Ke, Xiaoyan; Wang, Yong; Zimmer, Karina; Remke, Janet; Just, Annette; Nowak, Juliette; Schmidt, A; Pich, Andreas; Mazlan, S.M.I.; Reamon-Buettner, Stella Marie; Ramos, Gustavo; Frantz, Stefan; Viereck, Janika; Loyer, Xavier; Boulanger, Chantal M.; Wollert, Kai C.; Fiedler, Jan; Thum, Thomas

doi:10.1016/j.yjmcc.2020.07.001

Cited by 14 publications

(11 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These events require properly established ECM, which accommodates endothelial-mesenchymal transition, cell proliferation, and cell-cell adhesion in developing hearts (Kruithof, Krawitz, & Gaussin, 2007; Sullivan & Black, 2013; Von Gise & Pu, 2012). In adult murine hearts, where H19 has been well implicated in cardiac fibrosis and remodeling (Greco et al, 2016; Hobuß et al, 2020; Lee et al, 2011; Wang, Sun, & Sun, 2021), H19 overexpression led to increased ECM and fibrosis markers after myocardial injury, while deleting H19 resulted in downregulated ECM genes (Choong et al, 2019). In our +/ hIC1 endothelial cells, the expression of several key ECM genes such as Periostin (Postn ) (Snider, 2009; Sullivan, 2013), Col14a1 , and Adamts17 (Hubmacher, 2015) was significantly upregulated compared to wild-type cells.…”

Section: Discussionmentioning

confidence: 99%

DysregulatedH19/Igf2expression disrupts cardiac-placental axis during development of Silver Russell Syndrome-like mouse models

Chang

Fulmer

Hur

et al. 2022

Preprint

View full text Add to dashboard Cite

Dysregulation of the imprinted H19/IGF2 locus can lead to Silver-Russell Syndrome (SRS) in humans. However, the mechanism of how abnormal H19/IGF2 expression contributes to various SRS phenotypes remains unclear, largely due to incomplete understanding of the developmental functions of these two genes. We previously generated a mouse model with humanized H19/IGF2 ICR (hIC1) on the paternal allele that exhibited H19/Igf2 dysregulation together with SRS-like growth restriction and perinatal lethality. Here we dissect the role of H19 and Igf2 in cardiac and placental development utilizing multiple mouse models with varying levels of H19 and Igf2. We report severe cardiac defects such as ventricular septal defects (VSDs) and thinned myocardium, placental anomalies including thrombosis and vascular malformations, together with growth restriction in mouse embryos that correlated with the extent of H19/Igf2 dysregulation. Transcriptomic analysis using cardiac endothelial cells of these mouse models shows that H19/Igf2 dysregulation disrupts pathways related to extracellular matrix (ECM) and proliferation of endothelial cells. Our work links the heart and placenta through regulation by H19 and Igf2, demonstrating that accurate dosage of both H19 and Igf2 is critical for normal embryonic development, especially related to the cardiac-placental axis.

show abstract

Section: Discussionmentioning

confidence: 99%

DysregulatedH19/Igf2expression disrupts cardiac-placental axis during development of Silver Russell Syndrome-like mouse models

Chang

Fulmer

Hur

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Zhang et al [66] showed that plasma H19 was elevated in patients with CHD, and its level could serve as an independent predictor of CAD. Hobuss et al [67] found that H19 is upregulated in the acute phase after cardiac ischemia in mice, and in vitro cellular experiments found that hypoxia leads to upregulation of H19 in several cardiac cell types. Cao et al [68] found that H19 expression was elevated in human atherosclerotic plaques and oxidized-LDL (ox-LDL) treated HUVECs, and that H19 knockdown inhibited ox-LDL induced HUVEC inflammation, apoptosis, and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Differentially Expressed lncRNAs in the Perivascular Adipose Tissue of Patients with Coronary Heart Disease

Xie¹,

Wang²,

Rao³

et al. 2022

Rev. Cardiovasc. Med.

View full text Add to dashboard Cite

Background: Coronary heart disease is a highly prevalent inflammatory disease caused by coronary atherosclerosis. Numerous studies have revealed that perivascular adipose tissue is closely associated with atherosclerosis. Here, we conducted a comprehensive analysis of long non-coding RNAs and mRNAs differentially expressed in perivascular adipose tissue in patients with coronary heart disease. Methods: We conducted Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the differentially expressed genes. Furthermore, single sample gene set enrichment analysis, immune infiltration analysis, and co-expression analysis of differentially expressed long non-coding RNAs and immune gene sets were performed. Finally, the starBase and miRTarBase databases were used to construct a competing endogenous RNA network. Results: The results show that aortic perivascular adipose tissue has higher inflammation and immune infiltration levels in patients with coronary heart disease. Dysregulated long non-coding RNAs may be related to immunity, inflammation, and hypoxia. Conclusions: The findings of this study provide new insights into atherosclerosis and coronary heart disease.

show abstract

“…These events require properly established ECM, which accommodates endothelial-mesenchymal transition, cell proliferation, and cell-cell adhesion in developing hearts ( Kruithof et al, 2007 ; Sullivan and Black, 2013 ; von Gise and Pu, 2012 ). In adult murine hearts, where H19 has been well implicated in cardiac fibrosis and remodeling ( Greco et al, 2016 ; Hobuß et al, 2020 ; Lee et al, 2011 ; Wang et al, 2021 ), H19 overexpression led to increased ECM and fibrosis markers after myocardial injury, while deleting H19 resulted in downregulated ECM genes ( Choong et al, 2019 ). In our +/hIC1 endothelial cells, the expression of several key ECM genes such as Periostin ( Postn ) ( Snider et al, 2009 ; Sullivan and Black, 2013 ), Col14a1 , and Adamts17 ( Hubmacher and Apte, 2015 ) was significantly upregulated compared to wild-type cells.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated H19/Igf2 expression disrupts cardiac-placental axis during development of Silver-Russell syndrome-like mouse models

Chang

Fulmer

Hur

et al. 2022

eLife

View full text Add to dashboard Cite

Dysregulation of the imprinted H19/IGF2 locus can lead to Silver-Russell syndrome (SRS) in humans. However, the mechanism of how abnormal H19/IGF2 expression contributes to various SRS phenotypes remains unclear, largely due to incomplete understanding of the developmental functions of these two genes. We previously generated a mouse model with humanized H19/IGF2 imprinting control region (hIC1) on the paternal allele that exhibited H19/Igf2 dysregulation together with SRS-like growth restriction and perinatal lethality. Here, we dissect the role of H19 and Igf2 in cardiac and placental development utilizing multiple mouse models with varying levels of H19 and Igf2. We report severe cardiac defects such as ventricular septal defects and thinned myocardium, placental anomalies including thrombosis and vascular malformations, together with growth restriction in mouse embryos that correlated with the extent of H19/Igf2 dysregulation. Transcriptomic analysis using cardiac endothelial cells of these mouse models shows that H19/Igf2 dysregulation disrupts pathways related to extracellular matrix and proliferation of endothelial cells. Our work links the heart and placenta through regulation by H19 and Igf2, demonstrating that accurate dosage of both H19 and Igf2 is critical for normal embryonic development, especially related to the cardiac-placental axis.

show abstract

Pleiotropic cardiac functions controlled by ischemia-induced lncRNA H19

Cited by 14 publications

References 43 publications

DysregulatedH19/Igf2expression disrupts cardiac-placental axis during development of Silver Russell Syndrome-like mouse models

DysregulatedH19/Igf2expression disrupts cardiac-placental axis during development of Silver Russell Syndrome-like mouse models

Comprehensive Analysis of Differentially Expressed lncRNAs in the Perivascular Adipose Tissue of Patients with Coronary Heart Disease

Dysregulated H19/Igf2 expression disrupts cardiac-placental axis during development of Silver-Russell syndrome-like mouse models

Contact Info

Product

Resources

About